Un caso de leucemia cutánea / A case of cutaneous leukemia

Leucemia cutánea es una manisfestación extramedular de Leucemia. La frecuencia y edad de distribución depende del subtipo de leucemia1. Usualmente se presenta después que la enfermedad sistémica se ha manifestado y sugiere recaída o resistencia al tratamiento 11,12. Los hallazgos clínicos y morfológicos tienen una amplia variedad de manifestaciones y se pueden presentar en lesiones nodulares y placas. Raras manifestaciones incluyen máculas eritomatosas, ampollas y úlceras que pueden ocurrir solas o en combinación. A partir de una manifestación solitaria o en grupo, la leucemia cutis puede presentarse con rash eritematoso en un patrón clinicamente polimórfico. Consecuentemente , la leucemia cutánea debe distinguirse de diferentes diagnósticos diferenciales como por ejemplo: metástasis cutáneas o malignidades viscerales, linfoma, erupciones por fármacos, infecciones virales, sifilis, úlceras de varios orígenes. En la mucosa oral, hiperplasia gingival es el principal diagnóstico diferencial.1 El conocimiento de la morfologia clinica es de tremenda importancia en casos en donde la Leucemia no fuera conocida.1 Se presenta el caso poco frecuente de una paciente con diagnóstico de leucemia mieloide aguda que desarrolla una leucemia cutánea durante su seguimiento en Consulta Externa...(AU)

Cutaneous leukemia is an extramedullary manifestation of Leukemia. The frequency and age distribution depends on the subtype of leukemia1. It usually occurs after the systemic disease has manifested and suggests relapse or resistance to treatment 11,12. The clinical and morphological findings have a wide variety of manifestations and can occur in nodular lesions and plaques. Rare manifestations include erythematous macules, blisters and ulcers that can occur alone or in combination. From a solitary or group manifestation, leukemia cutis can present with erythematous rash in a clinically polymorphic pattern. Consequently, cutaneous leukemia must be distinguished from different differential diagnoses such as: cutaneous metastases or visceral malignancies, lymphoma, drug eruptions, viral infections, syphilis, ulcers of various origins. In the oral mucosa, gingival hyperplasia is the main differential diagnosis.1 The knowledge of the clinical morphology is of tremendous importance in cases where the Leukemia was not known.1 The rare case of a patient diagnosed with acute myeloid leukemia is presented that develops a cutaneous leukemia during its follow-up in Outpatient Consultation ... (AU)  

Seroprevalence and molecular epidemiology of human T-Cell leukemia virus type 1 (HTLV-1) and HTLV-2 in blood donors from Dakar, Senegal.

In 2002, human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 seroprevalence was 0.16% (8/4,900) in blood donors from Dakar, Senegal. Most of the positive donors originated from the country's southern region. Seven donors were infected by HTLV-1 (of cosmopolitan subtype), and one was infected by HTLV-2. These data highlight the problem of transfusion safety in this area where HTLV-1-associated lymphoproliferative and neurological diseases are endemic.

Residual risk of transfusion transmitted human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T lymphotrophic virus.

BACKGROUND: The risk of transfusion transmitted viral infection is now so low that mathematical modelling is required to estimate the residual risk. The first national viral risk estimates for hepatitis B virus (HBV), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were recently published by the Australian Red Cross Blood Service. Using several refinements to the original methodology, as well as an additional 2 years of data, new risk estimates have been derived. METHODS: Viral screening data for Australian donors for 2000/2003 were retrospectively analysed. The data were applied to three published models to estimate the residual risk of transmitting HIV, HBV, HCV or human T lymphotrophic virus (HTLV) by blood transfusion in Australia. RESULTS: Applying the three models to HBV, HIV and HCV, three point estimates of the residual risk per unit were calculated for each virus. The median point estimates were 1 in 1,339,000 for HBV, 1 in 1 in 7,299,000 for HIV, and 1 in 3,636,000 for HCV. Although the HTLV risk could not be equivalently calculated because of the lack of incident infection it was estimated to be considerably less than 1 in 1,000,000 using a separate method. CONCLUSIONS: The most current and accurate estimate of residual risk of viral transmission in Australia has been provided in the present study. The residual risk in Australia is exceptionally small, continuing to decrease and is generally less than European or US risk estimates. These new estimates demonstrate that for viral transmission the Australian blood supply is amongst the safest in the world, and provide a basis for evaluating the cost benefit of future viral testing methodologies.

[HTLV-I and HTLV-II virus]. / Virus HTLV-I et HTLV-II.

HTLV genomic and antigenic features, replication way as well as associated pathology are recalled herein. The epidemiologic angle and the different transmission ways are also related. HTLV infection diagnostic implements are detailed: screening and specially confirmatory tests are brought to light with the help of concrete examples interpreted according to the criteria defined by the Retrovirus Study Group of the French Blood Transfusion Society.

Relationship between anti-Tax antibody responses and cocultivatable virus in HTLV-I-infected rabbits.

The presence of anti-Tax antibody responses in human T cell leukemia virus type I (HTLV-I)-infected individuals has been correlated with increased proviral load, increased risk of transmitting infection, and increased risk of developing tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). In this study, a rabbit model of HTLV-I infection was used to determine whether anti-Tax antibody responses could predict the presence of virus with the potential to replicate. Seven of 14 HTLV-I-infected rabbits developed anti-Tax antibody responses. The onset of Tax reactivity was variable, but once detected remained constant throughout the remainder of the 60-week course of the study. All anti-Tax antibody positive rabbits produced virus as measured by p19 expression upon coculture, while p19 was detected in only one of the Tax antibody negative animals. Thus the presence of an anti-Tax antibody response correlates with p19 expression following cocultivation, and may be a useful predictor of virus replication in HTLV-I infected individuals.

A strategy for rapid, high-confidence protein identification.

A procedure is described for rapid, high-confidence identification of proteins using matrix-assisted laser desorption/ionization tandem ion trap mass spectrometry in conjunction with a genome database searching strategy. The procedure involves excision of copper-stained bands or spots from electrophoretic gels, in-gel trypsin digestion of the proteins, single-stage mass spectrometric analysis of the resultant mixture of tryptic peptides, followed by tandem ion trap mass spectrometric analysis of selected individual peptides, and database searching of the relevant genomic database using the program PepFrag. The scheme provides sensitive, real-time protein identification as well as facile identification of modifications. A single operator can unambiguously identify 5-10 proteins/day from an organism whose genome is known at a level of > 0.5 pmol of protein loaded on a gel. The utility of the technique was demonstrated by the identification and characterization of a band from a human HTLV-I preparation and 11 different proteins from a yeast RNA polymerase II C-terminal repeat domain-affinity preparation. The technology has great potential for postgenome biological science, where it promises to facilitate the dissection and anatomy of macromolecular assemblages, the definition of disease state markers, and the investigation of protein targets in biological processes such as the cell cycle and signal transduction.

Experimental bystander encephalitis induced by immunization with HTLV-I-producing T cells in mice.

ICR mice were immunized with HTLV-I carrier T lymphocytes (MT-2 cell line) and then inoculated intracerebrally with these cells. After non-specific traumatic hemorrhage, perivascular cell infiltration was noted diffusely throughout the brain on day 2 and lasted for over 2 weeks. HTLV-I antigens were detected in both sides of the cerebral hemisphere by Western blotting analysis. Tissue damage consisting of demyelination, axonal degeneration, and astrogliosis was observed most heavily on days 10 and 14. Non-immunized mice inoculated with the cells showed only transient hemorrhage. In cases using the HTLV-I free T-cell line (MOLT-4) inflammatory cell infiltration and tissue damage was much less conspicuous and disappeared after day 10. These experiments support the hypothesis that HAM/TSP is a bystander disease initiated and progresses via HTLV-I-infected T-cell invasion into the spinal cord of a patient who has been infected and sensitized to the virus.

Laboratory characterization of human T cell lymphotropic virus types 1 (HTLV-1) and 2 (HTLV-2) infections in blood donors from Sao Paulo, Brazil.

Serologic screening for human T cell lymphotropic virus types 1/2 (HTLV-1/2) infection in blood donors has been recently introduced in Brazil. Analysis of 351,639 blood donations in Sao Paulo from January 1992 to October 1993 identified 1,063 positive (0.30%) and 2,238 indeterminate (0.63%) samples based on serologic confirmation using a 21e Western blot. A detailed analysis (serologic, molecular, and virologic), based on a laboratory diagnostic algorithm for characterization of HTLV-1 and HTLV-2 infections was undertaken in 50 seropositive or seroindeterminate blood donors. Modified serologic assays (2.3 Western blot that incorporate type-specific recombinant peptides) performed in 29 HTLV-1/2 positive and 21 HTLV-1/2 indeterminate donors with the 21e Western blot identified 25 as infected with HTLV-1, four with HTLV-2, five with untypable HTLV-1/2, 15 as HTLV-1/2 indeterminate, and one as seronegative. Polymerase chain reaction (PCR) analysis using DNA amplification of proviral pol and tax sequences from peripheral blood mononuclear cells confirmed HTLV-1 and HTLV-2 infections in all 2.3 Western blot seropositive donors; of the five serologically untypable donors, three were confirmed to be HTLV-1 positive, one HTLV-2 positive, and one negative by PCR. All of the seroindeterminate donors were also negative by PCR. Furthermore, HTLV-1 could be isolated in cocultures from 10 of 18 infected donors. Cell lines developed from two HTLV-1-infected donors were of T cell phenotype (CD2+, CD3+), exhibiting surface markers of activated CD4 cells (CD4+ CD25+ HLA-DR+). Thus, we provide evidence for the high seroprevalence of HTLV infection in blood donor population in Sao Paulo, Brazil compared with North American donors and propose a comprehensive serologic and genotypic diagnostic algorithm for HTLV-infected donors that has strong implications for counseling of these individuals.

PIP: Blood donors in Brazil have recently begun to be screened for infection with HTLV types 1 and 2. Of 351,639 blood donations screened in Sao Paulo from January 1992 to October 1993, 1063 positive and 2238 indeterminate samples were identified based upon serologic confirmation using the 21e Western blot. Detailed serologic, molecular, and virologic analysis, based upon a laboratory diagnostic algorithm for the characterization of HTLV-1 and HTLV-2 infections, was conducted upon 50 seropositive or seroindeterminate blood donors. 2.3 Western blot serologic assays, which incorporate type-specific recombinant peptides, performed in 29 HTLV 1/2 positive and 21 HTLV 1/2 indeterminate donors with the 21e Western blot identified 25 as infected with HTLV-1, 4 with HTLV-2, 5 with untypeable HTLV 1/2, 15 as HTLV 1/2 indeterminate, and 1 as seronegative. Polymerase chain reaction (PCR) analysis using DNA amplification of proviral pol and tax sequences from peripheral blood mononuclear cells confirmed HTLV-1 and HTLV-2 infections in all 2.3 Western blot seropositive donors. Of the 5 serologically untypeable donors, 3 were found to be HTLV-1-positive, 1 HTLV-2-positive, and 1 negative by PCR. All seroindeterminate donors were also negative by PCR. HTLV-1 could be isolated in cocultures from 10 of 18 infected donors.

Human acute myeloid leukemias may be etiologically associated with new human retroviral infection.

The etiology of human acute myeloid leukemias (AML) remains uncertain. In order to examine the possibility of retroviral etiology in AML, we determined retroviral antigens related to HTLV-I in leukemic cell samples from 32 AML cases and peripheral blood mononuclear cells (PBMNCs) from 20 healthy donors by D-IGSS with high sensitivity and specificity, reverse transcriptase (RT) activity by a simple and sensitive non-radioisotopic RT assay, and retroviral particles by electron microscopy. The HTLV-I-related antigens were detected in 50.0% (16/32) of fresh leukemic cell samples and 87.5% (28/32) of cultured leukemic cell samples. The HTLV-I-related antigen-positive cells in fresh and cultured leukemic samples were 10.2% and 52.8%, respectively. Both frequency and level of HTLV-I-related antigens in cultured samples were much higher than in fresh samples. In contrast, no HTLV-I-related antigens were found in normal hematopoietic cells from 20 healthy donors. Further study results show that RT activity was detected not only in HTLV-I-related antigen-positive samples, but was also well correlated with the level of HTLV-I-related antigens in these samples, and preferred Mn+2 to Mg+2 as a cation. Moreover, typical retroviral particles were localized in most cultured HTLV-I-related antigen-positive samples by immunoelectron microscope. These data suggest that human acute myeloid leukemias may be etiologically associated with new human retroviral infection.

Anti-viral and immunomodulatory effects of interferon-alpha on cultured lymphocytes from patients with human T lymphotropic virus type I-associated myelopathy (HAM/TSP).

In contrast to therapeutic benefits of interferon-alpha (IFN-alpha) in patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the mechanisms underlying its clinical efficacy. To investigate the anti-viral and/or immunomodulatory properties of IFN-alpha in HTLV-I infection, the effects of IFN-alpha on HTLV-I-induced in vitro phenomena were evaluated. In vitro activation of HTLV-I in fractionated CD4+ T lymphocyte-rich cells (CD4+ cells) could be demonstrated by increased thymidine incorporation into the cells, detection of proviral HTLV-I and viral RNA, and by assays of reverse transcriptase activities in culture supernatants. T cell immune responses were evaluated by thymidine incorporation into CD8+ T lymphocyte-rich cells (CD8+ cells) responding to cultured and irradiated autologous CD4+ cells possessing HTLV-I antigens. It could be shown that IFN-alpha suppressed both the in vitro activation of HTLV-I and the CD8+ cell response. Moreover, 1 day supplementation of IFN-alpha as a pretreatment was sufficient for the induction of these properties. These findings, together with the clinical efficacy of IFN-alpha administration in patients with HAM/TSP, support the view that viral activation and T cell responses are critical components in the pathogenic processes involved in HAM/TSP.

A maternal risk factor for mother-to-child HTLV-I transmission: viral antigen-producing capacities in culture of peripheral blood and breast milk cells.

We examined the relationship between productivity of HTLV-I antigen-positive cells in cultured peripheral blood mononuclear cells (PBMC) and breast milk mononuclear cells (BMMC) and the incidence of mother-to-child transmission of HTLV-I. Among 61 cases of HTLV-I carrier mothers, 17 cases were revealed to produce large numbers of HTLV-I antigen-positive cells (high HTLV-I antigen-producing mothers) whose positive rate was 9.6% in PBMC and 10.2% in BMMC, while the remaining 44 cases produced small numbers of HTLV-I antigen-positive cells (low HTLV-I antigen-producing mothers) whose positive rate was 0.3% in PBMC and 0.5% in BMMC. The HTLV-I transmission rate among children born to the high HTLV-I antigen-producing mothers was 37.5% (6/16 children from 11 mothers), while that of the low HTLV-I antigen-producing mothers was 3.2% (1/31 children from 20 mothers). The transmission rate of HTLV-I was significantly different between high and low HTLV-I antigen-producing mothers (P < 0.05). However, there was no positive relationship between anti-HTLV-I antibody titers and productivity of HTLV-I antigen-positive cells (P = 0.11). These results suggested that mother-to-child transmission of HTLV-I might be influenced by a maternally determined factor to produce HTLV-I antigen-positive cells in PBMC and BMMC of HTLV-I carrier mothers.

The relationship between HTLV-I-infected cell lines and uveitis.

BACKGROUND: Recently it has been revealed that human T-lymphotropic virus type I (HTLV-I) infection causes uveitis in human. We previously reported HTLV-I uveitis in a rabbit. To investigate the relationship between HTLV-I infection and uveitis, we established an HTLV-I-infected T-cell clone from the cells infiltrated in the anterior chamber of this rabbit and compared the viral production with that in other HTLV-I-infected cell lines. METHODS: The clonality was determined by Southern blot hybridization with various restriction enzymes. Flow-cytometric analysis was used for investigating the expression of cell surface antigens. To compare viral production, we performed reverse transcriptase assay of the culture media and inhibition enzyme-linked immunosorbent assay to determine the quantity of intracellular HTLV-I antigens. RESULTS: The established clone was Ia (MHC class II) positive T cell. This T-cell clone was able to produce about three times more HTLV-I antigens than other HTLV-I-infected cell lines tested. CONCLUSION: A T-cell clone established from anterior aqueous of an HTLV-I uveitis rabbit can produce more HTLV-1 antigen than other HTLV-I-infected cell lines tested and it can be recognized easily by the immune system. Therefore, this high virus production may have a causal relation to uveitis.

Polymyositis in patients infected with human T-cell leukemia virus type I: the role of the virus in the cause of the disease.

To investigate the mechanism of polymyositis in human T-cell leukemia virus type I (HTLV-I) infection, we studied 6 HTLV-I-positive patients, 3 with polymyositis and 3 with adult T-cell leukemia but without clinical signs of muscle disease, by (a) quantitative single or double immunocytochemistry on serial 4-microns-thick muscle biopsy sections using antibodies to lymphocyte subsets, major histocompatibility complex (MHC) antigens, and HTLV-I proteins; (b) polymerase chain reaction using HTLV-I primers in the RNA and DNA extracted from 50 micrograms of muscle tissue or from serial 5-microns-thick fresh-frozen tissue sections; and (c) cocultures of the patients' HTLV-I-positive peripheral blood lymphocytes with their homologous muscles searching for replication of HTLV-I within the myotubes. In the muscle of patients with HTLV-I-associated myopathy, the predominant endomysial cells surrounding healthy muscle fibers were CD8+ cells followed by CD4+ cells and macrophages. MHC-I antigens were ubiquitous in the muscles of all 6 patients, even in those without endomysial inflammation. HTLV-I sequences were amplified from the whole muscle biopsy specimens but the cells harboring viral antigens were rare endomysial macrophages and not muscle fibers. Although HTLV-I sequences were amplified from all the patients' peripheral blood lymphocytes, these cells did not exert myotoxicity or resulted in viral replication in cocultures with their homologous myotubes.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of inhibitory effect of dextran sulfate and heparin on human T-cell lymphotropic virus type I (HTLV-I)-induced syncytium formation in vitro: role of cell-to-cell contact.

Cell-to-cell contact is usually essential for syncytium formation by HTLV-I-infected cell lines. The present study was undertaken to determine the inhibitory effect of polyanionic compounds, dextran sulfate and heparin, on HTLV-I-induced syncytium formation, as demonstrated by the fusion of HTLV-I-infected cells with target cells. These two compounds almost completely blocked syncytium formation in the early phase of the reaction at a concentration of 125 micrograms/ml, but dextran, as a control, did not inhibit it at concentrations up to 625 micrograms/ml. 50% inhibition of syncytium formation was detected at a concentration of 2 micrograms/ml of dextran sulfate 5000, 3 micrograms/ml of dextran sulfate 8000 and 8 micrograms/ml of heparin. The binding of radiolabeled HTLV-I-infected cells (HCT-1) to the target cells was inhibited by addition of dextran sulfate and heparin, and the inhibitory effects were concentration-dependent. No marked changes were detected in the expression of adhesion molecules on the virus-infected cells and target cells, and in the expression of envelope proteins on the virus-infected cells after exposing them to the polyanionic compounds. These results suggest that the blocking of cell-to-cell contact by polyanionic compounds, probably independent of surface adhesion molecules, is important for their inhibitory effect on HTLV-I-induced syncytium formation.

Presence of cross-reactive antibodies to HTLV-1 and absence of antigens in patients with multiple sclerosis.

Antibodies to HTLV-1, as determined by ELISA, were highly elevated in the serum samples of four out of four (100%) patients with TSP, moderately elevated in four out of four (100%) HTLV-1 carriers, slightly elevated in 12 out of 34 (35%) patients with MS, and absent from the serum samples of 34 normal subjects. Western blot analysis showed that the antibodies to HTLV-1 antigens in MS serum were heterogeneous. Cultivation of peripheral blood lymphocytes (PBLs) from patients with MS or normal subjects did not generate HTLV-1 core p19 antigen in the supernatant of culture medium, whereas cultivation of PBLs from patients with TSP and carriers of HTLV-1 generated core p19 antigen after 3 days for up to 28 days of cultivation. HTLV-1 antigens were also expressed on the surface of PBLs in three out of four patients with TSP and in two out of four HTLV-1 carriers on days 14 and 28 of cultivation, as measured by indirect immunofluorescence or alkaline phosphatase staining, but were not found in PBLs of any of 34 patients with MS or 34 normal subjects. The data indicate that although cross-reacting antibodies appear in the serum of some patients with MS, not enough evidence exists to suggest that HTLV-1 antigen is being produced in MS or that HTLV-1 plays a role in the pathogenesis of this disease.

Expression of the target antigen for cytotoxic T lymphocytes on adult T-cell-leukemia cells.

Adult T-cell-leukemia (ATL) cells were examined for susceptibility to human T-cell-leukemia virus type I (HTLV-I) tax-specific cytotoxic T lymphocytes (CTL) derived from a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). These CTL efficiently killed HLA-matched leukemia cells of an ATL patient after overnight incubation. However, ATL cells immediately after isolation from the peripheral blood were only marginally susceptible to the CTL. This is not due to inappropriate expression of major-histocompatibility-complex (MHC)-class-I antigen on the leukemia cells. Addition of synthetic peptide, corresponding to the CTL epitope, to the assay enabled the CTL to kill the fresh ATL cells. Scarcity of HTLV-I antigens in the fresh ATL cells and induction of these antigens by in vitro incubation were demonstrated both on the cell surface and in the cytoplasm. Lectin stimulation augmented synthesis of HTLV-I antigens, but was not essential for the induction. The presence in the culture of human plasma containing a high titer of antibodies to HTLV-I did not affect the induction of HTLV-I expression in the ATL cells. Furthermore, significantly lower levels of HTLV-I tax mRNA were present in the fresh ATL cells than in the cultured ATL cells, whereas the levels of HTLV-I proviral tax gene did not differ among these cells. This suppression of HTLV-I transcription in fresh ATL cells accounts for resistance to the CTL, and could be a reason for the persistence of HTLV-I infection in vivo.

In vitro infection of human macrophages with human T-cell leukemia virus type 1.

The tropism of the human T-cell leukemia virus type 1 (HTLV-1) for the cells of monocyte-macrophage lineage was evaluated by the coculture of blood monocyte-derived macrophages, with irradiated cells of HTLV-1 producing cell lines MT2 or C91/PL. The susceptibility to HTLV-1 was assessed by the detection of viral DNA using the polymerase chain reaction method. HTLV-1 gene expression in the cells was detected using in situ hybridization and by immunofluorescent staining of viral antigen. The presence of type C virus-like particles detected by electron microscopy and the ability to infect normal cord blood lymphocytes demonstrated that the infected macrophages produced infectious virus. These results indicate that human macrophages are susceptible in vitro to productive HTLV-1 infection, and thus might be involved in the pathogenesis of HTLV-1-related diseases.

Mixed connective tissue disease and Sjögren's syndrome, accompanied by HTLV-I infection.

A 48-year-old Japanese woman with mixed connective tissue disease (MCTD) and Sjögren's syndrome (SjS) was a carrier of HTLV-I and had anti-HTLV-I antibodies in her serum. Moreover, her peripheral blood lymphocytes contained proviral DNA for the pX region of HTLV-I as detected by the polymerase chain reaction. An immunohistological study was performed on her minor salivary gland to detect gene products of HTLV-I (P19 and P28 proteins); specific staining was demonstrated only in the epithelium of the salivary ducts. HTLV-I and its associated immune dysfunction may be responsible for MCTD and SjS in this patient.

No evidence for spumavirus or oncovirus infection in relapsing-remitting multiple sclerosis.

Polymerase chain reaction analysis was used to investigate the possible role of human spumaretrovirus and oncoretroviruses (human T-cell lymphotropic virus types I [HTLV-I] and II [HTLV-II]) in multiple sclerosis. Eleven patients with relapsing-remitting multiple sclerosis in exacerbation and 11 normal blood donors were included in the study. Cerebrospinal fluid cells, peripheral blood mononuclear cells, and plasma were cocultured with allogeneic mononuclear cells for 6 weeks. Cultured cells were subjected to polymerase chain reaction analysis with primers selected for the pol and gag (human spumaretrovirus), pol and env (HTLV-I), and pol (HTLV-II) genes. Polymerase chain reaction was negative in all patient and blood donor control samples, whereas positive controls were consistently reactive with high sensitivity. No culture exhibited cytopathic effects and supernatants were negative for reverse transcriptase activity. Thus, our results do not support a role for these retroviruses in the pathogenesis of multiple sclerosis.

Immune recognition of human T-cell leukemia virus type-I (HTLV-I) by MHC-restricted cytotoxic T lymphocytes.

In our studies, it was demonstrated for the first time that HTLV-I gag and pX, and env and pX antigens are the target antigens recognized by CD8+ CTL in association with RT-1k and RT-1l class I antigens, respectively, in the rat system. Furthermore, the gag-expressing rVV and the env-expressing rVV were shown to have the potential to induce HTLV-I-specific CTL in WKA and LEW rats, respectively. These results suggest that, in general, HTLV-I structural and non-structural antigens can be recognized by CTL, and their immunogenicity for the induction of HTLV-I-specific CTL may be influenced by host MHC. Successful vaccination of mice against retrovirus tumorigenicity with the viral structural components has been demonstrated. As was the case with polyoma virus-induced tumors, utilization of rVV vectors containing HTLV-I genes for potential HTLV-I vaccines in humans may become possible if target antigens recognized by each recipient CTL can be identified prior to vaccination. Another vaccine candidate will be a synthetic peptide containing each CTL epitope. We are currently identifying the CTL epitopes, and recent results indicate that a major CTL epitope on the env-gene product is located between the env amino acids 101-112 (Tanaka et al., manuscript in preparation).