The Content of ROS in Blood Lymphocytes of Healthy Individuals, Individuals Irradiated as a Result of Chernobyl Disaster and Patients with Prostate Cancer.

The ROS concentration and proliferation activity (Ki67 expression.marker) have been studied in the periphery blood lymphocytes of Moscow and Obninsk citizens, donors, Chernobyl disaster liquidators, inhabitants of the region contaminated after Chernobyl disaster (Klincy) and individuals with prostate cancer. It was shown that ROS concentration in lymphocytes of the liquidators and residents of the polluted region was lowered. But in lymphocytes of patients with tumors the ROS content was higher in comparison with the control. The cell content with Ki67 expression in lymphocytes of the individuals resided in the polluted region and tumor patients was lowered.

[Are the properties of peripheral blood lymphocytes of patients with prostate cancer connected with the efficiency of radiation therapy?].

The genome damage (frequency of cells with micronuclei and chromosome aberrations), concentration of reactive oxygen forms (ROS), markers of lymphocytes activation, expression of proliferation (CD69, Ki67) and proapoptotic antigen (CD95), as well as the ability to adaptive response have been investigated in blood lymphocytes of healthy donors and patients with prostate gland cancer. The influence of hormone-therapy on lymphocytes properties and connection between the parameters studied with the effectiveness of treatment, which was estimated by the level of prostate specific antigen (PSA), have been investigated. It was discovered that the genome damage to the patients with prostate gland cancer lymphocytes does not differ from control. The increase of the ROS level and decrease of radiosensitivity (irradiation of isolated lymphocytes in vitro at a dose of 1 Gy) are observed but they are insignificant. The content of the cells expressing CD69 and CD95 markers doesn't change but the expression of proliferative activity marker Ki67 in cells decreases. Radiosensitivity of lymphocytes in patients with prostate gland cancer correlates with the CD95 markers expression--a higher radio sensitivity points to their predisposition to apoptotic death. The expression of the markers studied depends on the oxidative status--a high ROS level suppresses their expression. The hormone therapy applied before radiotherapy leads to the increase in radiosensitivity and decrease in ROS. As the MN test shows, the ability to adaptive response of the lymphocytes in patients with prostate gland cancer is increased as compared with lymphocytes of healthy donors but it is insignificant; moreover, hormones do not influence the ability to the adaptive response. The high oxidative status further the formation of the adaptive response. We suppose that the discovered correlation between the initial, before treatment, frequency of lymphocytes with micronuclei and treatment effectiveness, namely, the decreased number of damaged cells associated with the treatment efficiency, is very important for the treatment prognosis. The results obtained can be very important for the experimental justification and understanding a possible use of blood lymphocytes for the additional diagnostics of prostate gland cancer and prognosis for its successful treatment.

[Dynamics of T-Cell receptor gene rearrangement and T-lymphocytes migration from thymus during post-radiation regeneration].

Recovery and migration of T-cells from the thymus to the secondary lymphoid organs in mice after sublethal gamma irradiation were investigated by measuring T-cell receptor excision circles (TRECs). The TRECs level practically represents the cellularity of thymus, in particular it correlates with the quantity of T-cells which have rearranged TCR genes and express the receptor complex CD3-TCR. So, TRECs can be considered as one of the markers of these cells. TREC-containing cells form a subset of recent thymic emigrants in the secondary lymphoid organs. After a significant TREC decrease in the lymph nodes within the early phase (4 days) after irradiation, we registered the increase of their number during urgent organ recovery due to T-cell migration from the thymus (the maximum is on the 10th day). The secondary thymic atrophy is accompanied by a weakening migration of the T-cells containing TRECs to lymph nodes. A significant TREC increase in the spleen was registered on the 4th day after irradiation. The rest of the recovery period. (up to 60 days) is characterized by the low TREC level. Thus, determination of TREC level allows obtaining additional information about recovery and migratory processes in lymphoid organs during post-radiation regeneration.

[Cytogenetic and immunological characteristics of stimulated human peripheral blood lymphocytes are connected with cell proliferation rates].

In the current study the authors investigated the connection between the proliferation rate of stimulated hu- man peripheral blood lymphocytes with some other characteristics of the population: expression of immunological markers, spontaneous genome damage, radiosensitivity. The population's proliferation index (PI) was taken as a measure of the rate. It was calculated using the composition of a cell population, which was cyto- kinesis-blocked with a cytochalasin B. If the genotoxic action is absent, the PI does not correlate with the spontaneous frequency of cells with micronuclei or with cell radiosensitivity, but is tightly linked with immunological indexes. It has been determined that after stimulation the level of marker-positive cells (CD25, CD69 and Ki67) is closely related to PI and is greater in the populations with lower proliferation rates. Irradiation of a cell culture 48 h after stimulation at a dose of 1 Gy leads to a correlation between PI and radiosensitivity, measured directly after the irradiation and in the same time frame as the PI measured in the non-irradiated population. The irradiated population's PI is not connected with the level of marker expression.

[Individual variability of immunological markers, radiosensitivity and oxidative status in blood lymphocytes of Moscow residents].

Expression of activation (CD69) and proliferation (Ki67) markers, their connection with each other, with the oxidative status (reactive oxygen species--ROS) and with radiosensitivity (determined by micronucleus test) have been studied on stimulated blood lymphocytes from Moscow inhabitants. It was shown that the content of T-lymphocytes with the expressed CD69 and the content of T-lymphocytes with the expressed Ki67 markers correlate (r = 0.571; p = 0.0004). We can suppose that expression of the CD69 marker (24 h after PHA stimulation) is needed for the cell cycle progression, but it is not enough for the high expression of Ki67 markers 48 h after stimulation (DNA synthesis phase). It was discovered that T-lymphocytes with the CD69 marker or T-lymphocytes with the Ki67 marker are connected by the negative correlation with the frequency of irradiated cell with micronucleus (MN) r = -0.487; p = 0.010; r = -0.440; p = 0.008, respectively. So we can suppose that lymphocyte radiosensitivity decreased with the increase of expression activation and proliferation markers. It was shown that radiosensitivity determined by MN test is not connected with the oxidative status determined by the reactive oxygen species content including superoxide anion radicals. It is possible to explain by the fact that the ROS concentration has been determined in non-stimulated lymphocytes, but frequencies of cells with MN - in the stimulated cells 48 h after stimulation. Using separate analysis of individual differences by the studied parameters that were determined in the same people, it was shown that individual differences are high enough in the same cases. For example, the radiosensitivity when cells were irradiated 48 h after stimulation, ROS concentration, cell content with activation and proliferation markers. In conclusion, we can say that we failed to find important correlation between the parameters studied. However, the presence of individual differences in the marker expression, the frequency of MN cells, the oxidative status in the usual inhabitants, typical donors in Moscow, is very important.

Neolactoferrin as a stimulator of innate and adaptive immunity.

The effect of the innovative product Neolactoferrin, a natural combination of recombinant human lactoferrin (90%) and goat lactoferrin (10%) isolated from the milk of transgenic goats carrying the full-length human lactoferrin gene, on human immune system cells was studied. Neolactoferrin enhanced the production of IL-1ß. Neolactoferrin saturated with iron ions increased the synthesis of pro-inflammatory cytokine TNFα. It determined the direction of the differentiation of precursor dendrite cells. Under the action of T cells, Neolactoferrin amplified the expression of the transcription factors responsible for the differentiation of Th- and Treg-cells and stimulated the production of both IFNγ and IL-4. The results suggest that Neolactoferrin exhibits an immunotropic activity and hinders the development of immune inflammatory processes. Iron saturation of Neolactoferrin increases its pro-inflammatory activity.

[The disturbances of the relationship between oxidative homeostasis and the immune status of lymphocytes in liquidators of the consequences of the Chernobyl accident].

We investigated into the relations between the immune status of individuals who took part in liquidating the consequences of the Chernobyl accident (liquidators) and the level of active oxygen forms in peripheral blood lymphocytes, as well as the level of the genome damage in lymphocytes (frequency of cells with micronuclei). The results show that the immune status changes as the level of the genome damage increases: the content of some markers increases and others decreases. It has also been shown that a) active oxygen forms participate in forming some indexes of the immunological lymphocyte status and b) the exposure of liquidators to irradiation many years ago almost completely changes the characteristics of the relation between the concentration of active oxygen forms and immunological status indexes. It has been shown that there are many more immunological indexes that experienced changes in their relation with the concentration of active oxygen forms than the amount of indexes associated with the genome damage. It has been found that a) there is little difference in the concentration of active oxygen forms in donors and liquidators and b) the concentration is not associated with the level of the genome damage. Taking this into account, the authors speculate that the changes in the relation between the concentration of active oxygen forms and the immunological indexes are reflection of how irradiation influences the level of the immune status formation based on the relation between the concentration of active oxygen forms and the appearance of a marker in the immune status. The obtained results point to the new, previously unknown aspects of how the primary injuries which are the result of the low dose irradiation influence the health of irradiated individuals. The changes in relations that can be seen in liquidators in comparison with donors lead to a different set of immunological indexes as well as to different immune status, and may become the reason for the deterioration in their health. The authors suppose that the above results could be a substantial contribution to the research into the fundamental mechanisms of the human immune status formation and human health.

[The epidemiological analysis of monitoring of the immune status in liquidators of consequences of the Chernobyl accident for early identification of risk groups and diagnostics of oncological diseases. Report 2. Dependence of frequency and changes in the immune status on risk factors of radiation accident].

Malignant neoplasms (MN) have been found to develop most frequently in the liquidators of entry into the ChNPP zones in 1986 (43.75%), as well as among the liquidators who worked for long, one quarter of whom participated in liquidation of the consequences of failure (LCF) in 1986. Specific features of the immune status depending on the timing of participation in LCF and the year of entry into the ChN PP zone have been established. Changes in the immune system in the persons with a confirmed diagnosis of MN who took both a non-permanent and permanent part in liquidating the consequences of the ChNPP failure in 1986 had the same character of deviations and differed in the magnitudes of deviations of immunological parameters. Continuous participation in the period of extreme conditions and a greater exposure to the radiation factor led to the increased content of CD8(+)-T-cells, CD16(+)-lymphocytes and activated T-lymphocytes, as well as to the reduced index of immune regulation, decreased content ofCD3-16/56+(NK)-cells (%) and the total IgE and to a greater deficiency of B-lymphocytes. Distinctions in the groups of liquidators who participated in LCF in 1986 and 1987 have been revealed. The greatest deviations in the IS indicators were found in liquidators-87. A similar effect came to light in case of a continuance in the ChNPP zones in 1986 and 1987; however, the degree of deviation of the content of CD4(+)-T-lymphocytes (41), CD8(+)-T-lymphocytes (1) and the immune regulation index (41) were remarkably higher in liquidators-87. A continuous stay in the ChNPP zones in 1987 led to the deficiency of CD4(+)-T-lymphocytes, increased values of CD8(+)-T-lymphocytes, a decreased index of CD4+/CD8+, as well as to the change in the ratio between NK-T and NK cells, increased numbers of CD95+, HLA-DR+ and activated T-lymphocytes, and a lower level of the total IgE. Long-term participation in LCF didn't cause any enhanced expression of cellular activation markers in liquidators-86. Specific features of changes in IS depending on a dose of external gamma-irradiation have been established. Increase in the frequency of MN among liquidators, in relation to the number of examinees in each age group, with age has been revealed. Distinctions in the age dynamics of IS in liquidators in the presence and in the absence of MN manifested themselves in a stable level of values of CD3+, CD4+, CD8(+)-T-lymphocytes, immune regulation index, CD95+, serum IgA at the age between 40 and 70 years old with a subsequent reduction in indicators and increase in the content of CD8(+)-T-lymphocytes with age in the absence of MN; continuous increase of CD3-16/56(+)-NK-cells in the presence of MN and decrease in the values after 70 in the absence of MN. Also revealed in IS of the both age groups of liquidators over 70 with and without MN was the deficiency of the T-cell component (CD3+, CD4(+)-T-lymphocytes, CD4+/CD8+ index) and the increase in absolute values of CD8(+)-T-lymphocytes. The growing deficiency of CD4(+)-T-lymphocytes during monitoring against the background of ever rising values of CD8(+)-T-lymphocytes leading to the weakening of the immune regulation due to progressing disorders of the T-lymphocyte regulatory subpopulation distribution can serve an indicator for the adverse prognosis of the life expectancy in the presence of MN.

[The epidemiological analysis of monitoring of the immune status in liquidators of consequences of the Chernobyl accident for early identification of risk groups and diagnostics of oncological diseases. Report 1].

Ionizing radiation is one of major factors of risk of oncological diseases. A question about the frequency of malignant neoplasms (MN) and their early identification in the liquidators of consequences of the Chernobyl accident remains opened. In the present work, the results of long-term immunological monitoring of the liquidators of consequences of the failure at the Chernobyl Nuclear Power Plant (ChN PP) living in the Northwest region of Russia are analyzed; we also heve made an attempt to reveal the predictors of oncological diseases in this group of individuals. The frequency of the newly revealed MN cases in a cohort of the persons who took part in liquidation of consequences of the ChNPP failure and were followed-up in 1999-2009, has made up 89 cases per 1005 persons (8.856%), which somewhat exceeds general population indicators. Regarding the frequency of separate MN localizations, lung cancer, cancer of stomach and cancer of prostate gland predominated, which corresponds to the world's tendency of MN prevalence. It has been established that as early as 1-3 years before diagnosis of MN is confirmed in liquidators, a number of changes in the immune status comes to light: drop in percentage of CD3+ and CD4(+)-T-lymphocytes, B-lymphocytes to a lesser extent, decrease in the CD4+/CD8+ index, increase of the relative and absolute content of CD16(+)-lymphocytes, increase of absolute content of CD8(+)-T-lymphocytes, prevalence of CD3+16/56+(NK-T) cell over CD3-16/56+(NK) cells, rise of the activity of phagocytes. Patients with the presence of one or several of the above-mentioned signs should be attributed to the MN risk group for determination of tumor markers, thorough examination and dynamic observation.

[The connection between molecular-cellular parameters and immune status of liquidators after Chernobyl accident].

The genome damage (the frequencies of cells with micronuclei (MN), chromosome aberrations, the level of DNA double-strand breaks (DSB DNA), the concentration of reactive oxygen species (ROS) and 28 immunological parameters have been studied on the blood lymphocytes of Chernobyl accident liquidators. The purpose of this article was the investigation of cytogenetic, molecular changes of blood lymphocytes of irradiated individuals 24 years after accident, examination it there are correlation between genome damage and immunological parameters. It was shown that in lymphocytes of liquidators the frequencies of cells with MN and with all type of chromosome aberrations didn't differ from the lymphocytes of nonirradiated individuals, but the frequency of chromosome aberration type was increased, the level of DSB DNA was increased too. The concentration of ROS is decreased. The percent of cytotoxic CD8(+)-T-lymphocytes, natural killer cells (CD16(+)-lymphocytes), CD3+ CD16+ CD56+ (NK-T-cells), that posses antivirus and antitumor activity--HLA-DR+, regulatory T-lymphocytes (CD4+ CD25+high) in liquidators significantly increases. The level of serum immunoglobulin (Ig A) significantly increases too. The index of immune regulation, meaning of phagocyte neutrophil (FAN) and macrophage activity decreases. In liquidators there are significant correlation between the frequencies of cells with MN and the content of regulatory T-lymphocytes (p < 0.05), between the concentrations of ROS and activated T-lymphocytes. More connection is on the tendency level (p < 0.10): the frequency of chromosome aberrations, the DSB DNA level with natural killer cells and regulatory T-lymphocytes; the frequency of cells with MN and DSB DNA and FAM. We can suppose that genomic instability induced by the liquidators of Chernobyl accident consequences 24 years ago manifests now as increased genome damage and oxidative status decrease that can result in imbalance of cells and humoral immune status, disturbancies of health.

Ex vivo stimulation of cord blood mononuclear cells by dexamethasone and interleukin-7 results in the maturation of interferon-gamma-secreting effector memory T cells.

The effects of dexamethasone phosphate and interleukin-7 upon the proliferation of T-cells and the production of interferon-gamma in the newborn's cord blood mononuclear cell cultures were studied. The capability of dexamethasone to enhance T-cell proliferation induced by anti-CD3 with interleukin-7 in some newborn cord blood mononuclear cell cultures was identified. Dexamethasone suppressed production of interferon-gamma in 68-h cell cultures stimulated with anti-CD3 both in the presence of interleukin-7 and without it. However, a 68-h cultivation of newborn blood cells with dexamethasone, anti-CD3 and interleukin-7 resulted in the accumulation of T-lymphocytes capable of producing interferon-gamma after restimulation. As a result of it the amount of interferon-gamma producing CD7(+) T-cells and the concentration of interferon-gamma in cultural supernatants were maximal in the cell cultures incubated with anti-CD3, interleukin-7 and dexamethasone during the first 68 h and subsequently restimulated with phorbol 12-myristate 13-acetate and ionomycin. The stimulation of neonatal or adult blood cells by dexamethasone, anti-CD3 and interleukine-7 also causes a decrease in the number of naïve T-cells and central memory cells and an increase in the number of effector memory CD7(+)CD45RA(+)CD62L(-) cells in cultures. It is possible that these effects are caused by the influence of dexamethasone on IL-7 receptor expression: it is known that IL-7 receptor alpha-chain gene is a glucocorticoid-inducible gene.

[In vivo and vitro effects of interferon-alpha 2b on functional activity of T-lymphocytes from patients with rheumatoid arthritis]. / Vliianie alpha2b-interferona in vivo i in vitro na funktsional'nuiu aktivnost' T-limfotsitov bol'nykh revmatoidnym artritom.

AIM: To investigate the effect of recombinant alpha 2b-interferon (r alpha 2b-IFN) on functional capacity of peripheral blood (PB) T cells in rheumatoid arthritis (RA) patients and the relationship between functional characteristics of T lymphocytes and the disease activity. MATERIALS AND METHODS: PB mononuclear cells (PBMC) were separated by Ficoll-Verografine++ gradient centrifugation from 24 healthy donors (HD) and 75 RA patients 19 of which were treated with r alpha 2b-IFN (realdiron, Biofa, Lithuania) in the dosage 1 million IU i.m. each other day for 20 days, 10 injections a course. Cell surface markers (CD3, CD4, CD8) and adhesion molecules (CD18, CD54, CD2) were analyzed using specific monoclonal antibodies (MoAbs) and flow cytometry on the PBMC, freshly isolated and treated for 72 hours with medium alone, PHA, r alpha 2b-IFN and their combination. The proliferative response of PBMC to MoAbs for CD3, PHA and r alpha 2b-IFN were assessed by 3H-thymidine incorporation. The percentage of spontaneous and inducing apoptosis was quantified by flow cytometry using propidium iodide staining. RESULTS: The expression of CD18 was lower on RA PB lymphocytes compared to HD PB lymphocytes (p < 0.05). After stimulation of PBMC in both RA patients and HD with PHA, percentages of CD2+, CD3+, CD4+, CD18+ cells significantly diminished (p < 0.05), whereas the percentages of CD54+ and CD18+ (p < 0.05) cells increased. We have found three types of RA PB lymphocytes response to complex factors in vitro: 1) the presence of the proliferative response to T-mitogens but not to r alpha 2b-IFN (56% of the patients); 2) the presence of the increased proliferative response to T-mitogens and r alpha 2b-IFN (17% of the patients); 3) the absence of the proliferative response to T-mitogens and r alpha 2b-IFN (27% of the patients). PBMC of HD demonstrate only the first type of the response. R2 alpha b-IFN demonstrated own mitogenic effect and increased mitogen-induced proliferation in PBMC cultures with a high proliferative response to T-mitogens. The levels of spontaneous and inducing apoptosis were increased in RA PB lymphocytes compared to HD. After stimulation with PHA, RA PB lymphocytes preferentially underwent apoptosis whereas cells of HD proliferated. High disease activity correlated positively with an increase of a proliferative response to mitogens and apoptosis and a decrease in the percentage of lymphocytes, expressed adhesion molecules. The treatment with r alpha 2b-IFN induces changes in T-cell response to mitogens similarly to those after incubation with r alpha 2b-IFN in vitro before treatment. CONCLUSION: Functional capacity of RA PB lymphocytes relates to the disease activity. Inhibitory or stimulatory effects of r alpha 2b-IFN depend on functional activity of RA lymphocytes. Using the test with alpha 2b-IFN incubation, we may predict changes of apoptosis and proliferation levels caused by different agents in RA lymphocytes after treatment with r alpha 2b-IFN.

[Interferon therapy effects on activation of T-lymphocytes in patients with systemic lupus erythematosus]. / Vliianie terapii interferonom na aktivatsiiu T-limfotsitov bol'nykh sistemnoi krasnoi volchankoi.

AIM: To elucidate the effects of combined therapy with glucocorticosteroids (GCS) and recombinant human interferon alpha or gamma (IFN) on proliferative responses of T-lymphocytes activated by various surface molecules (CD3 and CD2) in patients with SLE. MATERIALS AND METHODS: A 3-month trial entered 3 groups 15 patients each with verified SLE by APA criteria (1982). Patients of group 1, 2 and 3 received IFN-alpha (realdiron, Biofa, Lithuania) in a single dose 3 million IU i.m., IFN-gamma (inflagen, Biofa, Lithuania) in a single dose 3 million IU i.m. and cyclophosphamide in a dose 200 mg i.m. once a week, respectively. T-lymphocyte proliferative response was assessed to stimuli of two types: CD3-dependent (classic activation) and CD2-dependent (alternative activation). The analysis was made by inclusion of 3H-thymidine after 72-hour incubation of peripheral blood mononuclear cells with various stimuli. The response was assessed before the treatment, on the treatment day 20 and after the treatment. The blood from 27 donors was also examined. Flow cytometry estimated the percentage of the cells expressing molecules CD3, CD4, CD8. RESULTS: The effect is found of alpha and gamma INF on functional capacity of T-lymphocytes and on the number of cells expressing surface molecules CD3 and CD4. Realdiron produced two-phase reaction to a proliferative response to mitogenic stimuli by CD3-dependent activation pathway: the initial rise then lowering. CD2-dependent way of T-cell activation is associated with weakening of responses to all combinations of stimuli with participation of autologous red cells. This group of patients to the end of the therapy exhibited a significant decrease in the number of cells expressing CD3 and CD4 (p < 0.05 and p < 0.001, respectively). Inflagen enhanced CD3-dependent activation of T cells and normalized the response to all types of the alternative stimuli. This group demonstrated an increase in the number of cells expressing CD3 and CD4 (p < 0.01 and p < 0.05, respectively). The changes in the number of CD8+ cells in both the groups were statistically insignificant. The controls had T-cell responses reduced by both activation pathways. CONCLUSION: Preparations of both alpha and gamma interferon have a multidirectional influence on functional potential and phenotype of T-lymphocytes of SLE patients.

[Clinico-immunological and allergological characteristics of population of the Middle ural]. / Kliniko-immunologicheskaia i allergologicheskaia kharakteristika zhitelei Srednego Urala.

Clinical investigation of immune and allergic state of 633 adult dwellers of the Middle Ural region was carried out. The first (occupational) group consisted of 479 workers of the industrial plant, most of which exposed to negative factors such as radiation, harmful chemical substances and stress. The second (control) group consisted of 154 town-dwellers, who did not work at the industrial plant. Immune state was assessed in 714 people. Clinical symptoms of immune deficiency were found in 67% of the occupational group and in 76% of the control group. Allergic condition and allergic-infection syndrome were common for both groups, the rate of infection syndrome being relatively low. The immune state of the occupational group showed in comparison to control reliable increase in absolute and relative amount of T-lymphocytes, in the ratio CD4+/CD8+ and in the level of serum IgG. It was found also the decrease in the concentration of T-killers, the amount of NK cells and B-lymphocytes, phagocyte activity and the level of serum IgA. It was suggested that regional and ecological peculiarities influence the immune state rather than induce clinical symptoms of immune deficiency.

[The classical and alternative pathways of T-lymphocyte activation in patients with systemic lupus erythematosus]. / Sostoianie klassicheskogo i al'ternativnogo putei aktivatsii T-limfotsitov u bol'nykh sistemnoi krasnoi volchanki.

AIM: To study activation of T-lymphocytes by the CD3 (antigen-dependent) and CD2 (non-antigen-dependent) routes in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Peripheral blood mononuclears were studied in 66 patients with SLE and 27 donors. Proliferative response to activation by anti-CD3, anti-CD3+ phorbol-12-myristate-13-acetate (PMA), phytohemagglutinin (PHA), and autologous erythrocytes in combinations with PMA and recombinant interleukin-2 (rIL-2) was assessed. RESULTS: T-cell proliferation was at least two times increased under the effect of CD3 in 40.9% patients and in 100% normal subjects. Stimulation with CD3 antibodies in combination with PMA leveled the differences due to boosting of T-cell response in SLE patients. PMA alone caused mononuclear proliferation in 25% patients with SLE but not in normal subjects. Decreased response of T-cells to adhesive stimulus (autologous erythrocytes + PMA) in SLE patients was leveled by rIL-2. CONCLUSION: The proliferative response of T-lymphocytes is decreased upon stimulation with CD3 and CD2 and in some patients increased by PMA in submitogenic doses, added alone or in combination with anti-CD3.

The resistance of activated T-cells from SLE patients to apoptosis induced by human thymic stromal cells.

In this paper we show the differential sensitivity of phytohemagglutinine (PHA) activated T-cells from healthy donors or patients with systemic lupus erythematosus (SLE) to apoptosis induced by human thymic stromal cell line of epithelial origin. T-cells from SLE patients were mainly resistant to the apoptotic action of the stromal cells, while normal T-lymphocytes readily died via apoptosis. Gel electrophoresis revealed a DNA fragmentation pattern characteristic of apoptosis after 18 h of coculture. The simultaneous measurement of [3H]-thymidine uptake showed that the proliferative response of T-cells from SLE patients was significantly decreased compared to their normal counterparts. Such difference may account for the distinct result of interactions between the stromal and lymphoid cells, leading to the subsequent survival of T-lymphocytes from SLE patients. Nevertheless pretreatment of normal activated T-lymphocytes with anti-Fas mAbs, which have the capacity to substantially inhibit signaling through this receptor resulted in abolition of this form of programmed cell death. Thus, the precise role of Fas receptor and its ligand in this in vitro test system needs further investigation.

[Changes in the immune system of the victims of the action of the factors in the accident at the Chernobyl Atomic Electric Power Station. Their manifestations, nature and the possible sequelae]. / Izmeneniia v immunnoi sisteme postradavshikh ot deistviia faktorov avarii na ChAES. Proiavleniia, priroda, vozmozhnye posledstviia.

The hypothesis is formulated, which explains genesis of long-lasting disturbances in the immune system of the persons affected by factors of Chernobyl disaster. Immunological alterations which are displayed at the late time after action of radiation in doses 0.5 Gy or lower are not a result of direct damage of the cells of immune system by irradiation. Their development is more probably a result of appearance of some systemic conditions and factors in affected organism--such as hormonal disbalance and especially autoantibodies of different specificities, including those reactive with thymic epithelial cells. Autoantibodies of the last type induce the decrease of thymic hormone secretion which results in functional deficiency of T lymphocytes. This chain of events is similar to those occurring in aging and does not directly causes development of the clinical displays of immunodeficiency. Only irradiation in doses of 4-6 Gy or higher inducing the structural damage of thymic microenvironment can rouse the long-lasting T cell immunodeficiency with the clinical manifestations.

[Immune status of adult population of the Bryansk region living in territory polluted by radionuclides]. / Immunnyi status vzroslogo naseleniia Brianskoi oblasti, prozhivaiushchego na territoriiakh, zagriaznennykh radionuklidami.

Clinical and immunological investigation with immune status evaluation of three groups of adult population of Bryansk Region was performed. The first group included 165 persons living in Vyshkov (settlement of town type in Bryansk Region) contaminated with radionuclides as a result of Chernobyl accident. The second group included 68 persons living in Vyshkov, immunological monitoring of those was performed. The third group consisted of 114 persons living on the "clean" area of Pochep (Bryansk Region). On both areas (contaminated Vyshkov and "clean" Pochep) the large percent of persons (three quarters of all investigated ones) had clinical manifestations of immune deficiency. The immune status of Vyshkov inhabitants was characterized by T-helper/inductor activation. That was expressed in significant increase of CD4+, CD4+/CD8+ in comparison of control group of primary donors and to "clean" Pochep inhabitants and in stable decrease of average values of serum IgG in comparison to control group, IgG and IgM in comparison to Pochep group. Maximum high values of T-helpers under lowest T-suppressor/killer values were observed at clinical symptoms which may be stipulated by radiation factor (loss of hair and teeth, surplus weight, predisposition to bleedings) and in persons working in cattle-breeding.