Markers of T Cell Exhaustion and Senescence and Their Relationship to Plasma TGF-ß Levels in Treated HIV+ Immune Non-responders.

Background: Immune non-responders (INR) are HIV+, ART-controlled (>2 yrs) people who fail to reconstitute their CD4 T cell numbers. Systemic inflammation and markers of T cell senescence and exhaustion are observed in INR. This study aims to investigate T cell senescence and exhaustion and their possible association with soluble immune mediators and to understand the immune profile of HIV-infected INR. Selected participants were <50 years old to control for the confounder of older age. Methods: Plasma levels of IL-6, IP10, sCD14, sCD163, and TGF-ß and markers of T cell exhaustion (PD-1, TIGIT) and senescence (CD57, KLRG-1) were measured in ART-treated, HIV+ participants grouped by CD4 T cell counts (n = 63). Immune parameters were also measured in HIV-uninfected, age distribution-matched controls (HC; n = 30). Associations between T cell markers of exhaustion and senescence and plasma levels of immune mediators were examined by Spearman rank order statistics. Results: Proportions of CD4 T cell subsets expressing markers of exhaustion (PD-1, TIGIT) and senescence (CD57, KLRG-1) were elevated in HIV+ participants. When comparing proportions between INR and IR, INR had higher proportions of CD4 memory PD-1+, EM CD57+, TEM TIGIT+ and CD8 EM and TEM TIGIT+ cells. Plasma levels of IL-6, IP10, and sCD14 were elevated during HIV infection. IP10 was higher in INR. Plasma TGF-ß levels and CD4 cycling proportions of T regulatory cells were lower in INR. Proportions of CD4 T cells expressing TIGIT, PD-1, and CD57 positively correlated with plasma levels of IL-6. Plasma levels of TGF-ß negatively correlated with proportions of TIGIT+ and PD-1+ T cell subsets. Conclusions: INR have lower levels of TGF-ß and decreased proportions of cycling CD4 T regulatory cells and may have difficulty controlling inflammation. IP10 is elevated in INR and is linked to higher proportions of T cell exhaustion and senescence seen in INR.

Relevance of anti-HNK1 antibodies in the management of anti-MAG neuropathies.

INTRODUCTION: In peripheral neuropathies with antibodies against Myelin Associated Glycoprotein (MAG), an IgM monoclonal gammopathy recognizes a specific epitope called Human Natural Killer 1 (HNK1) shared by NK lymphocytes and several components of the peripheral nerve myelin. Recently an ELISA test has been developed to detect antibodies against HNK1 epitope. Objectives were to determine the usefulness of this assay in the management of anti-MAG neuropathy. METHODS: Anti-HNK1 antibodies were assessed with the GanglioCombi™ MAG ELISA test (Buhlmann) in 41 anti-MAG neuropathies and in 118 controls: 34 chronic inflammatory demyelinating polyradiculoneuropathies, 3 Miller Fisher syndromes, 12 sensory neuronopathies, 63 length-dependent axonal sensory polyneuropathies, 6 healthy controls. Anti-HNK1 antibody was tested before and 1 year after rituximab therapy in seven patients with anti-MAG neuropathy. RESULTS: Anti-HNK1 antibodies were positive in 40/41 anti-MAG neuropathies, and in 1/118 controls (sensitivity 98%, specificity 99%). Only considering controls with IgM paraprotein, specificity was 96% (23/24). In anti-MAG neuropathies, anti-HNK1 titre was correlated with sensory deficiency evaluated with the INCAT sensory sum score (r = 0.4, p = 0.01) and with disability evaluated with the Rasch-built Overall Disability Scale (r = [Formula: see text] 0.4, p = 0.01) and Overall Neuropathy Limitation Scale (r = 0.4, p = 0.02). Anti-HNK1 titres were not related to age, disease duration, atypical clinical features and anti-MAG antibodies titres. Anti-MAG titres were not associated with disease severity. Anti-HNK1 titres were decreased by 18% 1 year after rituximab treatment. CONCLUSIONS: Anti-HNK1 antibodies have good sensitivity and specificity for the diagnosis of anti-MAG neuropathy. Interestingly, anti-HNK1 titres are related to the disease severity and decrease after rituximab infusions.

Decreased Expression of the CD57 Molecule in T Lymphocytes of Patients with Chronic Fatigue Syndrome.

The chronic fatigue syndrome (CFS) is characterized by a prolonged incapacitating fatigue, headaches, sleep disturbances, and decreases in cognition, besides alterations in other physiological functions. At present, no specific biological markers have been described in this pathology. In the present study, we analyzed in lymphocytes the CD57 expression for the diagnosis of CFS, evaluating both the percentage of blood lymphocytes expressing CD57 and the average amount of the molecule expressed per cell. The study demonstrated a marked and significant decrease in the expression of CD57 in lymphocytes of CFS patients regarding healthy controls. In T lymphocytes, the decrease was significant both in the percentage of cells expressing CD57 (7.5 ± 1.2 vs 13.3 ± 1.6, p = 0.024) and in a more relevant way in the amount of CD57 molecule expressed per cell (331 ± 59 vs 1003 ± 104, p ≤ 0.0001). In non-T lymphocytes, the decrease was significant only in the amount of CD57 expressed per cell (379 ± 114 vs 691 ± 95, p = 0.007). The study of CD57 antigen in blood lymphocytes is a useful marker that could cooperate in the diagnosis of CFS patients. Its decrease in T lymphocytes provides most valuable results than the results in other lymphocyte subpopulations.

Cytotoxic Natural Killer Subpopulations as a Prognostic Factor of Malignant Pleural Effusion.

BACKGROUND: Malignant pleural effusion (MPE) is a sign of advanced disease of poor prognosis. As natural killer (NK) cells are involved in the first line of tumour defence, we aimed to validate a new diagnostic and prognostic indicator for MPE based on NK subpopulations of pleural fluid (PF) and peripheral blood (PB). METHODS: NK subpopulations were determined in PF and PB in 71 patients with malignant, paramalignant or benign pleural effusion. The receiver operating characteristic (ROC) curves, Kaplan-Meier, multivariable Cox model and decision trees created with the CHAID (Chi-square automatic interaction detector) methodology were employed. RESULTS: We demonstrated that the PF/PB ratios of the CD56 bright CD16- and CD56 dim CD16- NK subpopulations were higher (p = 0.013 and p = 0.003, respectively) in MPEs and paramalignant pleural effusions (PPEs) than in benign ones, with an AUC of 0.757 and 0.741, respectively. The PF/PB ratio of CD16+ NK and CD57+ NK obtained a higher hazard ratio (HR) in the crude Cox's regression analysis. In the adjusted Cox's regression analysis, the PF/PB ratio of CD16+ NK gave the highest HR (HR 6.1 [1.76-21.1]) (p = 0.004). In the decision tree created for the MPE prognosis, we observed that the main predictor variable among the studied clinical, radiological, and analytical variables was lung mass, and that 92.9% of the patients who survived had a PF/PB ratio of the CD56 dim CD16+ NK subpopulation ≤ 0.43. CONCLUSIONS: Our data suggest that both the PF/PB ratios of cytotoxic subpopulations CD57+ NK and CD16+ NK are useful as a prognostic factor of MPE. Other subpopulations (CD56 bright CD16- and CD56 dim CD16- NK) could help to diagnose MPE.

Features of peripheral CD8+CD57+ lymphocytes in patients with autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) is an acquired condition characterized by the presence of autoantibodies recognizing erythrocyte-related antigens. Several components of the immune system are involved in disease pathogenesis. Among them, as for other autoimmune disorders, a role for specific CD8+CD57+ regulatory cells subset could be hypothesized. We evaluated this lymphocyte subset by flow cytometry in 18 AIHA patients randomly selected in a retrospective population of 29 cases. Secondary forms were observed in 65.5% of cases, whereas frequencies of warm, cold, mixed, and atypical forms were similar. Cold agglutinins and cryoglobulins tested positive in 44.8% and 10.3% of cases, respectively. These patients exhibited a higher frequency of peripheral vascular symptoms (odds ratio = 8.2, p = .04) and complement consumption (odds ratio = 7.2, p = .02). Frequency of CD8+CD57+ cells resulted significantly higher in AIHA patients than in control group (17.0 ± 15.8% vs 8.2 ± 5.0%, p = .04). Regardless of therapeutic schedule, patients with partial or no response to therapy (8/18) showed higher frequencies of CD8+CD57+ cells as compared with controls (23.6 ± 21.3% vs 8.9 ± 4.9%, p = .01), whereas 10/18 complete responders (CR) showed lower levels of CD8+CD57+ cells (11.7 ± 6.9%, p = .11). CR and controls showed similar values (p = .24). This study suggests that monitoring this lymphocyte subset before and after treatment administration might have a prognostic value. Moreover, CD8+CD57+ cells may represent a possible therapeutic target to restore the normal balance between lymphocyte populations.

Alloimmune responses and atherosclerotic disease after kidney transplantation.

BACKGROUND: Chronic exposure to exogenous antigens causes accumulation of proinflammatory CD57(+)CD28(-) hyperactivated CD8(+) T cells that may promote atherosclerosis. We hypothesized that persistent alloimmune responses may induce immune activation and contribute to posttransplant atherosclerosis. METHODS: This hypothesis was tested in a single-center cohort of 577 kidney transplant patients. Propensity score analysis was performed to address potential confounding variables by indication. Immune exhaustion was studied in subcohort of 103 patients. RESULTS: Five hundred seventy-seven consecutive renal transplant recipients were included. Seventy-seven atherosclerotic events (AE) (12.3%) occurred during a mean follow-up of 7 years. The cumulative incidence of AE increased with the number of human leukocyte antigen (HLA) mismatches (18%, 10%, and 5% in patients with 5-6, 3-4, and 0-2 mismatches, respectively; P=0.012). Human leukocyte antigen mismatch number (hazards ratio, 1.35; 95% confidence interval, 1.10-1.66, for each supplementary mismatch; P=0.005) was an independent risk factor for AE. In the propensity score match analysis, having received a well-matched kidney conferred a reduced risk of AE (hazards ratio, 0.22; 95% confidence interval, 0.05-0.95; P=0.044). We observed a significant correlation between HLA mismatch numbers and circulating CD57(+)CD28(-) CD8(+) T cells (R=0.31; P=0.017). These CD8(+) T cells were more frequent in patients with more HLA mismatches (P<0.0001). CONCLUSION: Overall, our results suggest that chronic allogeneic stimulation participates to accelerated atherosclerosis observed after transplantation.

Characterization of CD8(+)CD57(+) T cells in patients with acute myocardial infarction.

Although T cells are known to be involved in the pathogenesis of coronary artery disease, it is unclear which subpopulation of T cells contributes to pathogenesis in acute myocardial infarction (MI). We studied the immunological characteristics and clinical impact of CD8(+)CD57(+) T cells in acute MI patients. The frequency of CD57(+) cells among CD8(+) T cells was examined in peripheral blood sampled the morning after acute MI events. Interestingly, the frequency of CD57(+) cells in the CD8(+) T-cell population correlated with cardiovascular mortality 6 months after acute MI. The immunological characteristics of CD8(+)CD57(+) T cells were elucidated by surface immunophenotyping, intracellular cytokine staining and flow cytometry. Immunophenotyping revealed that the CD8(+)CD57(+) T cells were activated, senescent T cells with pro-inflammatory and tissue homing properties. Because a high frequency of CD8(+)CD57(+) T cells is associated with short-term cardiovascular mortality in acute MI patients, this specific subset of CD8(+) T cells might contribute to acute coronary events via their pro-inflammatory and high cytotoxic capacities. Identification of a pathogenic CD8(+) T-cell subset expressing CD57 may offer opportunities for the evaluation and management of acute MI.

CD4+ T-cell deficiency in HIV patients responding to antiretroviral therapy is associated with increased expression of interferon-stimulated genes in CD4+ T cells.

Most patients with human immunodeficiency virus (HIV) who remain CD4(+) T-cell deficient on antiretroviral therapy (ART) exhibit marked immune activation. As CD4(+) T-cell activation may be mediated by microbial translocation or interferon-alpha (IFN-α), we examined these factors in HIV patients with good or poor CD4(+) T-cell recovery on long-term ART. Messenger RNA levels for 3 interferon-stimulated genes were increased in CD4(+) T cells of patients with poor CD4(+) T-cell recovery, whereas levels in patients with good recovery did not differ from those in healthy controls. Poor CD4(+) T-cell recovery was also associated with CD4(+) T-cell expression of markers of activation, senescence, and apoptosis, and with increased serum levels of the lipopolysaccharide receptor and soluble CD14, but these were not significantly correlated with expression of the interferon-stimulated genes. Therefore, CD4(+) T-cell recovery may be adversely affected by the effects of IFN-α, which may be amenable to therapeutic intervention.

CD57 expression by T cells in the female genital tract of HIV-zx1 infected women.

Despite an influx of T cells to the cervix during HIV infection, genital T cells are not associated with control of HIV shedding. CD57 expression by T cells has been associated with enhanced migratory potential and CD57+ T cells have been shown to accumulate in tissues during the late stages of HIV disease. We investigated the impact of HIV-infection and clinical status on the expression of CD57 by T cells from the female genital tract in 13 HIV-infected and 5 uninfected women. We found that cervical and blood-derived T cells expressed similar frequencies of CD57. The frequency of CD57 expression by cervical or blood T cells was not associated with clinical status (CD4 counts). No impairment in IFN-gamma production by CD57+ T cells from the genital tract was observed. We conclude that increased T cell senescence does not appear to be a hallmark of genital mucosal HIV-1 infection.

Peripheral blood CD8highCD57+ lymphocyte levels may predict outcome in melanoma patients treated with adjuvant interferon-alpha.

BACKGROUND: The objective of this study was to evaluate the significance of CD8highCD57+ lymphocytes for the survival of high risk melanoma patients treated with adjuvant interferon-alpha (IFN-alpha). PATIENTS AND METHODS: The prognostic significance of peripheral blood CD8highCD57+ lymphocyte levels for survival was analysed retrospectively in 16 IFN-alpha-treated melanoma patients with resected regional lymph node metastases. The survival of the patients was analyzed using the Kaplan-Meier method. The difference between survival curves was determined using the log-rank test. RESULTS: The median survival time of patients with >23% CD8highCD57+ lymphocytes prior to treatment with IFN-alpha was 14.2 months, whereas the median survival time of patients with < 23% CD8highCD57+ lymphocytes was not reached at the time of analysis (median follow-up 24.6 months). CONCLUSION: Larger prospective studies are justified to investigate the precise value of CD8highCD57+ lymphocytes in the selection of melanoma patients for adjuvant treatment with IFN-alpha.

Definition of adult-onset rheumatoid arthritis from elderly-onset rheumatoid arthritis by studying T-lymphocyte subpopulations, their soluble receptors and soluble receptor of interleukin-2.

AIMS: The study of the distribution of T-lymphocyte sub-populations has revealed some immune characteristics of rheumatoid arthritis (RA) as well as polymyalgia rheumatica (PMR). There is much evidence that the subsets of T-lymphocyte subpopulations are well correlated with the age of the patient and the precise diagnosis of RA and PMR. The aims of the study were to evaluate the absolute number and percentage of T-lymphocyte subpopulation subsets in peripheral blood and their soluble receptors and serum soluble receptors of interleukin-2. MATERIAL AND METHODS: Thirty-six patients with RA were divided into 21 adult-onset RA (AoRA) and 15 elderly-onsets RA (EoRA) patients. They were compared with 48 PMR patients, 21 normal subjects under 45 years and 17 healthy elderly subjects over 65 years. T-lymphocyte subsets were studied by FACSCAN with double stained specific monoclonal antibodies. The EL ISA method was used to determine soluble receptors of CD4+ and CD8+ and IL-2. RESULTS: The AoRA patients had a significant alteration of T-lymphocyte sub-populations as well as their specific soluble receptors compared to EoRA patients. On the other hand, distribution of T-lymphocyte sub-populations in EoRA patients was quite similar to that in PMR patients. CONCLUSIONS: This method is probably not applicable for daily routine clinical practice but provides some interesting data for differential diagnosis between RA and PMR.

BY55/CD160 cannot be considered a cytotoxic marker in cytomegalovirus-specific human CD8(+) T cells.

CD160/BY55 is a glucosyl-phosphatidylinositol (GPI)-anchored cell membrane receptor that is expressed primarily in natural killer (NK) cells. Its presence in CD8(+) T lymphocytes is considered to be a marker of cytotoxic activity, although there are few data in this regard. In the present work, we analysed the expression of CD160 in subpopulations of cytomegalovirus (CMV)-specific CD8(+) T cells. Subpopulations were defined by CD28 and CD57 expression and exhibited varying degrees of differentiation and cytotoxic potential, as evaluated by the expression of perforin, interferon (IFN)-gamma and interleukin (IL)-7Ralpha/CD127. We included subjects with different intensities of anti-viral immune response. Results showed that the terminally differentiated CD28(-) CD57(+) subset displaying the highest level of perforin expressed CD160 at a level similar to that of memory CD28(+) CD57(-)perforin(-) cells. A comparison of the expression of perforin in CD160(+) cells versus CD160(-) cells showed that expression was significantly higher in the absence of CD160. Interestingly, the CMV-specific CD8(+) T cell subset from a patient with ongoing CMV reactivation did not begin to express CD160 until day +92 of the follow-up period. Taken together, our data show that CD160 cannot be considered a cytotoxic marker in CMV-specific CD8(+) T cells.

Thoracoscopic talc poudrage decreases T-lymphocytes in the peripheral blood.

BACKGROUND: Thoracoscopic talc poudrage induces peripheral blood granulocytosis and lymphopenia. The aim of this study is to investigate the type of lymphopenia in patients undergoing thoracoscopic talc poudrage. METHODS: We have measured peripheral blood lymphocyte subsets in 11 patients undergoing thoracoscopic talc poudrage, before (baseline), at 24 and 48 h after the procedure. Lymphocyte numbers were analysed by flow cytometry for the evaluation of the CD3+, CD4+, CD8+ cells (total T-lymphocytes, helper T-lymphocytes, cytotoxic T-lymphocytes, respectively), the CD19+ cells (B-lymphocytes), and the CD16+, CD56+ and CD57+ cells (NK-cells). No anti-inflammatory medication was permitted before, during or after the procedure. RESULTS: Absolute peripheral blood lymphocyte count significantly decreased following thoracoscopic talc poudrage compared to baseline values (p=0.007). Similarly, peripheral blood CD3+, CD4+ and CD8+ lymphocyte counts significantly decreased compared to baseline (p=0.005, 0.02 and 0.03, respectively) with a more prominent reduction of CD3/CD45RO memory cells. No significant difference was found in the absolute number of CD19+, CD16+, CD56+, and CD57+ cells before and after thoracoscopic talc poudrage. CONCLUSION: Patients undergoing thoracoscopic talc poudrage display peripheral blood T-lymphopenia following the procedure.

Increased expression of CD30 and CD57 molecules on CD4(+) T cells from children with atopic asthma: a preliminary report.

T helper type 2 (Th2) cells play an important role in the onset and persistence of allergic airway inflammation. Consequently, many authors have attempted to identify cell surface markers associated with a Th2 phenotype. This work was aimed at correlating CD30 and CD57 expression on CD4(+) T cells with interleukin (IL)-4 production in peripheral blood mononuclear cells (PBMCs) from allergic patients. PBMCs from 17 children with atopic asthma and 12 nonatopic healthy control children were analyzed. The CD28, CD30, CD40L, CD57, CD62L, CD69, IL-4, and IFN-gamma expressions on CD4(+) T cells were determined by double immunofluorescence and flow cytometry in PBMCs ex vivo and after phorbol-12-myristate-13-acetate plus ionomycin (PMA/I) stimulation. An increased percentage of peripheral CD4(+)CD30(+) T cells was observed in asthmatic patients (p < 0.001). In addition, the percentage of CD4(+) T cells expressing IL-4, IFN-gamma, CD30, CD40L, CD57, or CD69 significantly increased (p < 0.01) after PMA/I stimulation, in asthmatic patients. The CD30 expression on CD4(+) T cells from asthmatic patients, after stimulation, correlated with both IL-4 and IFN-gamma production, whereas CD57 expression only correlated with IL-4 production. These data suggest that the expression of CD30 and CD57 cell markers on T cells could reflect circulating effector T cell early activation in the allergic airway disease.

Maintenance of HIV-specific CD4+ T cell help distinguishes HIV-2 from HIV-1 infection.

Unlike HIV-1-infected people, most HIV-2-infected subjects maintain a healthy CD4+ T cell count and a strong HIV-specific CD4+ T cell response. To define the cellular immunological correlates of good prognosis in HIV-2 infection, we conducted a cross-sectional study of HIV Gag-specific T cell function in HIV-1- and HIV-2-infected Gambians. Using cytokine flow cytometry and lymphoproliferation assays, we show that HIV-specific CD4+ T cells from HIV-2-infected individuals maintained proliferative capacity, were not terminally differentiated (CD57-), and more frequently produced IFN-gamma or IL-2 than CD4+ T cells from HIV-1-infected donors. Polyfunctional (IFN-gamma+/IL-2+) HIV-specific CD4+ T cells were found exclusively in HIV-2+ donors. The disparity in CD4+ T cell responses between asymptomatic HIV-1- and HIV-2-infected subjects was not associated with differences in the proliferative capacity of HIV-specific CD8+ T cells. This study demonstrates that HIV-2-infected donors have a well-preserved and functionally heterogeneous HIV-specific memory CD4+ T cell response that is associated with delayed disease progression in the majority of infected people.

Beneficial effects of protein-bound polysaccharide K plus tegafur/uracil in patients with stage II or III colorectal cancer: analysis of immunological parameters.

Protein-bound polysaccharide K (PSK) increased the 5-year disease-free survival rate and reduced the risk of recurrence in a randomised, controlled study for stage II and III colorectal cancer. In order to elucidate the disease-free survival benefits with PSK and what immunological markers could indicate a PSK responder, serial changes in immunological parameters were monitored in the study. PSK decreased the mean serum immunosuppressive acidic protein (IAP) level, and increased the mean population of natural killer (NK) cells compared with the controls. The 5-year disease-free and overall survival rate for patients with serum IAP values or=8% at 3 months after surgery, PSK conferred a significantly better (p=0.038) 5-year disease-free survival (86.7%; 95% CI: 74.5-98.8%) compared to the control group (60.0%; 95% CI: 29.6-90.4%). In the proportional hazards model, the presence of regional metastases (relative risk, 3.595; 95% CI: 1.518 to 8.518; p=0.004) and omission of PSK treatment (relative risk, 3.099; 95% CI: 1.202 to 7.990; p=0.019) were significant indicators of recurrence. PSK acts as an immunomodulatory activity and biochemical modulator in stage II or III colorectal cancer. Pre-operative serum IAP values or=8% at 3 months after surgery are possible PSK response predictors.

Apoptosis of CD57+ and CD57- lymphocytes in the lung and blood of HIV-infected subjects.

Patients infected with HIV frequently have a CD8+ lymphocytic alveolitis consisting of HIV-specific CD8+CD57- cytotoxic T lymphocytes. However, in late stage disease, there is expansion of a CD8+CD57+ population with suppressive properties. We examined role of lymphocyte apoptosis in the expansion of the CD8+CD57+ lymphocytes in late stage HIV in the lung and blood compartment in human subjects. Fas was expressed on virtually all lung lymphocytes from HIV-infected and normal subjects. Fas ligand expression was increased in HIV infection in both CD8+CD57+ and CD8+CD57- lymphocytes, though a significantly greater percentage of CD8+CD57+ cells expressed this marker. CD8+CD57+ lymphocytes in normal and HIV-infected subjects underwent more apoptosis than CD8+CD57- cells. However, in late stage HIV infection, the percentage of CD8+CD57+ cells undergoing apoptosis declined. These data demonstrate that under normal conditions CD8+CD57+ cells appear destined to undergo programmed cell death. Expansion of suppressive CD8+CD57+ cells in the lungs of HIV-infected subjects with advanced disease may be due to the failure of this normal regulatory process.

Acute lymphoblastic leukemia with coexpression of CD56 and CD57: case report.

The authors present the clinical profile of a 6-year-old girl with an unusual immunophenotype of acute lymphoblastic leukemia (ALL). At the initial presentation, massive hepatosplenomegaly developed. The leukemic cells were myeloperoxidase-negative and morphologically lymphoblastic. These cells were positive for B-precursor-cell (CD10, CD19) antigens and natural killer cells (CD56, CD57). Rearrangements of both immunoglobulin heavy chain alleles and monoallelic rearrangement of T-cell receptors (TCRs)-beta and -delta genes, but not that of TCR-gamma gene, were detected, suggesting that these cells being of B-precursor origin. The patient received chemotherapy for extremely high-risk ALL with a good response. To the authors' knowledge, this is the first pediatric case describing coexpression of CD56 and CD57 on B-lineage ALL.

Expansion of peripheral CD8+ T cells in patients with coronary artery disease: relation to cytomegalovirus infection.

OBJECTIVES: The nature of the immune response in coronary artery disease (CAD) is not fully defined. One pathogen that has been linked to atherogenesis, cytomegalovirus (CMV), is known to exert strong and long-lasting effects on peripheral T cells. In the present study, we investigated the effect of prior CMV infection on the immune system in CAD patients. SUBJECTS: Patients with stable angina and angiographically verified CAD (n=43) and clinically healthy controls (n=69) were included. METHODS: The expression of CD57 and CD28 on peripheral CD4+ and CD8+ T cells was evaluated with three-colour flow cytometry. The findings were related to serological markers of inflammation, T-cell activation and CMV seropositivity. RESULTS: An expansion of CD8+ T cells expressing CD57 but lacking CD28 was seen in the patient group. The numbers of CD8+ CD57+ and CD8+ CD28-T-cell subsets were independently related to CMV seropositivity (P<0.001) but also to CAD per se (P<0.05). Serum concentrations of C-reactive protein (CRP) and soluble interleukin-2 receptor (sIL-2R) were elevated in the patients but not related to CMV or CD8+ T-cell subsets. CONCLUSION: A pronounced shift in peripheral T-cell homeostasis was observed in CAD patients. Primarily CMV infection but also CAD per se contributed to the expansion of CD8+ T-cell subsets. The T-cell changes were not related to a systemic inflammatory response but should rather be considered as markers of a chronic antigen exposure and/or immunosenescence in CAD.