Early Effects of HTLV-1 Infection on the Activation, Exhaustion, and Differentiation of T-Cells in Humanized NSG Mice.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy of CD4+ T-cells associated with HTLV-1 infection. In this study, we used the model of immunodeficient NSG mice reconstituted with a functional human immune system (HIS) to investigate early events in HTLV-1 pathogenesis. Upon infection, human T-cells rapidly increased in the blood and lymphoid tissues, particularly CD4+CD25+ T-cells. Proliferation of CD4+ T-cells in the spleen and mesenteric lymph nodes (MLN) correlated with HTLV-1 proviral load and CD25 expression. In addition, splenomegaly, a common feature of ATLL in humans, was also observed. CD4+ and CD8+ T-cells predominantly displayed an effector memory phenotype (CD45RA-CCR7-) and expressed CXCR3 and CCR5 chemokine receptors, suggesting the polarization into a Th1 phenotype. Activated CD8+ T-cells expressed granzyme B and perforin; however, the interferon-γ response by these cells was limited, possibly due to elevated PD-1 expression and increased frequency of CD4+FoxP3+ regulatory T-cells in MLN. Thus, HTLV-1-infected HIS-NSG mice reproduced several characteristics of infection in humans, and it may be helpful to investigate ATLL-related events and to perform preclinical studies. Moreover, aspects of chronic infection were already present at early stages in this experimental model. Collectively, we suggest that HTLV-1 infection modulates host immune responses to favor viral persistence.

An Unusual Association of Adult T-Cell Leukemia/Lymphoma With Hyalohyphomycosis.

Infection by human T-cell lymphotropic virus (HTLV-1) causes deregulation of the immune system, which makes the infected individuals more susceptible to infectious diseases. Immune deregulation is even more pronounced in HTLV-1 carriers with adult T-cell leukemia/lymphoma (ATLL), which results in frequent opportunistic infections. Hyalohyphomycosis is a rare subcutaneous mycosis which is more commonly associated with immunocompromised patients. We report a case of a HTLV-1-infected man with skin tumors, inguinal lymphadenomegaly, and lymphocytosis. Histopathological examination of skin biopsies revealed a T-cell lymphoma intermingled with a granulomatous process with abscesses and hyaline-septated hyphae. The lymph node showed only a T-cell lymphoma. The patient was diagnosed with acute ATLL and hyalohyphomycosis. He was treated with itraconazole for the subcutaneous mycosis and with chemotherapy for ATLL. A few months later, despite the treatment, he died because of progression of ATLL.

Treatment of strongyloidiasis in HTLV-1 and Strongyloides stercoralis coinfected patients is associated with increased TNFα and decreased soluble IL2 receptor levels.

BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) infection has been associated with recurrent and disseminated strongyloidiasis and adult T cell leukemia/lymphoma (ATLL). METHODS: We compared immunological aspects and markers for ATLL in HTLV-1 patients with or without strongyloidiasis, and evaluated the influence of Strongyloides stercoralis treatment on the immune response and clinical outcomes of HTLV-1 infection. RESULTS: Levels of TNFα and IFNγ were lower in patients coinfected with HTLV-1 and S. stercoralis than in patients with HTLV-1 only (p < 0.05), and there was an increase in TNFα levels after anthelmintic treatment. Levels of sIL-2R were higher in patients with HTLV-1 coinfected with S. stercoralis and anthelmintic treatment decreased sIL-2R levels (p < 0.05). The one patient who developed ATLL was coinfected with S. stercoralis. CONCLUSION: These data show that helminthic infection has a modulatory role in HTLV-1 infection and that S. stercoralis may be a cofactor in the development of ATLL.

Are increased Foxp3+ regulatory T cells responsible for immunosuppression during HTLV-1 infection? Case reports and review of the literature.

Research of human T lymphotropic virus type I (HTLV-1)-associated diseases is mostly focused on inflammatory and lymphoproliferative disorders. However, the immunosuppressive consequences of HTLV-1 infection are frequently ignored. In developing countries where exposure to parasitic and other tropical diseases is frequent, the burden of disease is significantly increased by opportunistic infections. Regulatory T cells (Tregs) are a CD4 T-cell subset capable of suppressing effector responses. During HTLV-1 infection, CD4+Foxp3+ cells are increased in HTLV-1-associated leukaemia/lymphoma (ATLL) as well as in non-leukaemic presentations. However, controversy exists regarding the actual regulatory function of these cells. In this report, we present two cases of HTLV-1 ATLL complicated by parasitic organisms and we provide a brief review of the literature regarding FoxP3+ regulatory T cells and their role as a possible mechanism for the immunosuppressive manifestations that take place during HTLV-1 infection.

In contrast to HIV, KIR3DS1 does not influence outcome in HTLV-1 retroviral infection.

While most carriers of human T-cell leukemia virus type 1 (HTLV-1) remain asymptomatic throughout their lifetime, infection is associated with the development of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The exact parameters that determine these outcomes are unknown but are believed to include host genetic factors that control the immune response to infection. Host response to fellow retroviridae member HIV is influenced by the expression of members of the Killer Immunoglobulin Receptor (KIR) family including KIR3DS1. In this study we examined the association of KIR3DS1 with the outcome of HTLV-1 infection in three geographically distinct cohorts (Jamaican, Japanese and Brazilian). Despite increased prevalence of KIR3DS1 in the HAM/TSP patients of the Jamaican cohort, we found no evidence for a role of KIR3DS1 in influencing control of proviral load or disease outcome. This suggests that unlike HIV, KIR3DS1-mediated regulation of HTLV-1 infection does not occur, or is ineffective.

Quantitative differences in HTLV-I antibody responses: classification and relative risk assessment for asymptomatic carriers and ATL and HAM/TSP patients from Jamaica.

Adult T-cell leukemia (ATL) and human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are known to be caused by HTLV-I infection. However, current methods used to determine HTLV-I infection do not differentiate between HTLV-I asymptomatic carriers (ACs) and ATL and HAM/TSP patients. Using the luciferase immunoprecipitation system, a highly sensitive, quantitative technology that can efficiently detect HTLV-I Ab responses, we examined Ab responses for HTLV-I in serum/plasma samples from 439 subjects in Jamaica, including HTLV-I-seronegative donors, ACs, and ATL and HAM/TSP patients. The Ab responses of HTLV-I-infected subjects differed significantly from those of seronegative donors for all 3 immunodominant proteins, Gag, Env, and Tax. HAM/TSP patients had significantly higher Ab responses for Gag and Env compared with ACs, and Ab responses for all 3 Ags were higher in HAM/TSP patients than in ATL patients. Moreover, immunoreactivities for HTLV-I Ags as determined by the luciferase immunoprecipitation system could distinguish HAM/TSP patients from ACs at a true-positive rate of 85.42% and from ATL patients at a true-positive rate of 75.00%, and modeled in conjunction with subject information to distinguish HAM/TSP patients from ACs (odds ratio = 14.12) and from ATL patients (odds ratio = 7.00). The relative risk assessment resulting from these significant differences between Ab responses in HTLV-I-infected groups may be a useful diagnostic tool in the future.

Adult T-cell leukemia/lymphoma (ATL) presenting in the skin: clinical, histological and immunohistochemical features of 52 cases.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is a severe disease caused by HTLV-I. This paper describes the clinicopathological and immunohistochemical findings of 52 cases of ATL with skin involvement and investigates whether there is any relationship between median survival time (MST) and histological patterns, primary cutaneous involvement and CD8 positivity. MATERIAL AND METHODS: All cases were HTLV-I+ and HIV- and were clinically classified. HTLV-I proviral integration was investigated in atypical cases. Immunohistochemistry was performed using CD3, CD4, CD5, CD7, CD8, CD20, CD25, CD30 and CD45RO markers. Ki-67 was used to evaluate the proliferative index. RESULTS: Twenty-seven cases were primary, while 25 were secondary. Monoclonal viral integration was demonstrated in all atypical cases. Patterns resembling mycosis fungoides (MF) were found in 19 cases and anaplastic large-cell lymphoma (ALCL) in two cases. Fifteen cases had an atypical immunophenotype and expressed CD8. Primary cutaneous ATL had a longer MST (48 months) than the secondary cutaneous ATL (7 months) and the difference was statistically significant, but no statistically significant difference was found between the MST of CD8-positive and negative cases. CONCLUSIONS: It is important to differentiate between primary and secondary cutaneous ATL and classify the cases histologically in order to better evaluate the prognosis. The two forms of primary cutaneous ATL, primary cutaneous smoldering and primary cutaneous tumoral (PCT), should also be identified. The smoldering type presented a longer survival (58 months) and histological aspects suggestive of better prognosis in contrast to the PCT type that had a shorter survival (20 months) and histological characteristics suggestive of worse outcome.

[Viral Tax protein expression in salivary glands of patients infected with human t-cell lymphotropic virus type I and Sicca Syndrome]. / Proteína Tax (HTLV-I), probable factor patogénico y marcador del síndrome sicca que se asocia a HAM/TSP.

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) is a retrovirus that influences cellular metabolism modifying biological responses. This results in oncogenic, degenerative or inflammatory changes. The myelopathy associated to HTLV-I or tropical spastic paraparesia (HAM/TSP) is a mainly degenerative response to the virus infection. On the other hand, Sjögren syndrome has an inflammatory appearance. The immunohistochemical study of CD-4, CD-8 and CD45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein in pathological samples of salivary glands may help to differentiate primary from viral Sicca syndrome. AIM: To perform an immunohistochemical study of salivary glands of patients with HAM/TSP and Sicca syndrome and control subjects. MATERIAL AND METHODS: Pathological samples of salivary glands from 53 patients with HAM/TSP and Sicca syndrome and 10 control subjects, were studied. Immunohistochemistry was performed using antibodies against CD-4, CD-8 and CD-45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein. RESULTS: Only in patients with HAM/TSP and Sicca syndrome, the presence of Tax protein was observed in CD-4 and CD-8 lymphocytes and in glandular acini. CONCLUSIONS: Patients infected with HTLV-I express Tax protein in salivary glands. This finding has diagnostic and pathogenic implications.

Proteína Tax ( HTLV-I ), probable factor patogénico y marcador del síndrome sicca que se asocia a HAM/TSP / Viral Tax protein expression in salivary glands of patients infected with human t-cell lymphotropic virus type I and Sicca Syndrome

Background: Human T-cell lymphotropic virus type I (HTLV-I) is a retrovirus that influences cellular metabolism modifying biological responses. This results in oncogenic, degenerative or inflammatory changes. The myelopathy associated to HTLV-I or tropical spastic paraparesia (HAM/TSP) is a mainly degenerative response to the virus infection. On the other hand, Sjögren syndrome has an inflammatory appearance. The immunohistochemical study of CD-4, CD-8 and CD45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein in pathological samples of salivary glands may help to differentiate primary from viral Sicca syndrome. Aim: To perform an immunohistochemical study of salivary glands of patients with HAM/TSP and Sicca syndrome and control subjects. Material and Methods: Pathological samples of salivary glands from 53 patients with HAM/TSP and Sicca syndrome and 10 control subjects, were studied. Immunohistochemistry was performed using antibodies against CD-4, CD-8 and CD-45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein. Results: Only in patients with HAM/TSP and Sicca syndrome, the presence of Tax protein was observed in CD-4 and CD-8 lymphocytes and in glandular acini. Conclusions: Patients infected with HTLV-I express Tax protein in salivary glands. This finding has diagnostic and pathogenic implications.

Clonally rearranged T-cell receptor beta chain genes in HTLV-I carriers with abnormal, non-flower-like, lymphocytes.

BACKGROUND: The diagnosis of Adult T-cell leukemia/lymphoma ATLL subtypes in human T-lymphotropic virus type I (HTLV-I) carriers based in morphology and immunophenotype of lymphocytes can be challenger. We propose that polymerase chain reaction (PCR) amplification of the rearranged TCR gene in HTLV-I healthy carriers would be a convenient method for establishing the nature of the circulating T lymphocytes in asymptomatic HTLV-I carriers, presenting only mild and inconclusive signals of deviation from normality. METHODS: Using PCR, we analyzed the genetic recombination pattern of the T-cell beta-chain receptor gene (TCR-beta) in order to identify clonal expansion of peripheral blood T lymphocytes in 17 HTLV-I-positive healthy carriers and in nine normal HTLV-I-negative blood donors. To evaluate the performance of PCR in detection of clonality, we also analyzed 18 patients with post-thymic/mature T-cell malignancies presenting circulating abnormal lymphocytes. RESULTS: Seven of the 17 HTLV-I positive individuals presented circulating abnormal lymphocytes; monoclonal or oligoclonal expansion of T-cells was detected in five of the 17 HTLV-I-positive individuals, all of them presenting abnormal lymphocytes. Clonal expansion was not detected in any of the negative controls or in any of the 12 remaining healthy carriers. All patients in the positive control group tested positive by PCR and Southern blots. Southern blots were negative for all 17 healthy carriers. CONCLUSIONS: PCR amplification of segments of rearranged TCR-beta is reliable for allowing early detection of small populations of clonal T cells in blood samples from asymptomatic HTLV-I carriers, providing an additional alert in the follow-up of carriers with abnormal circulating lymphocytes.

The first report of familial adult T-cell leukemia/lymphoma in Argentina.

Here we describe two Caucasian brothers who developed adult T-cell leukemia/lymphoma (ATLL), within a short period of time. These two patients have never left Argentina. Their parents are dead and according to the family history it is possible that the mother may have been affected by spastic paraparesis. The daughters reported that their mother had suffered from increasing difficulty in walking for many years which finally made it impossible for to her walk. There are no other data to support the presumptive diagnosis. One of the patients presented with acute disease while the other had a lymphoma type disorder. Both were positive for HTLV 1. The first patient died with disease progression ten months after diagnosis and the second is in partial remission 13 months after diagnosis. Immunophenotyping showed CD4+, CD5+, CD3+, CD2+, CD8 (-). Two asymptomatic brothers with positive HTLV 1 serology were detected. This is the first family case that has been reported in Argentina.

[Immunophenotyping of acute lymphoblastic leukemia in Mexican children]. / Inmunofenotipo de la leucemia aguda linfoblástica en niños mexicanos.

PURPOSE: To analyse the immunophenotype of leukaemic cells in a group of children diagnosed of lymphoblastic leukaemia in order to assess the frequency of the different immunologic subtypes. PATIENTS AND METHODS: In the period comprised between APR 1987 and MAR 1995, 402 Mexican children were studied in a prospective way. Conventional immunological markers were used, either associated to or specific for B, T, myelo-monocytic or megakaryocytic-platelet cell populations. RESULTS: Five major immunologic subtypes were disclosed, showing a series of specific surface markers: null-ALL, 5%; early pre-B, 7.5%; common, 74.6%; B-cell, 3.5%, and T-cell, 9.4%. A net predominance of B-cell precursor CD10- ALL was found in children under one year of age, and of CD10+ B-cells beyond that age. Although there was only slight predominance of male sex, the prevalence of B and TALL in males was not confirmed. CONCLUSIONS: These results show that the incidence of the different immunologic subtypes of lymphoblastic leukaemias and their distribution according to age and sex are closely similar to those reported among Caucasians in other parts of the world.

Leucemia linfoma T del adulto en Chile: estudio clínico patológico y molecular de 26 pacientes / Adult T cell leukemia lymphoma in Chile: a clinical-pathological and molecular study of 26 patients

Background: Adult T cell leukemia lymphoma is a lymphoproliferative syndrome etiologically associated to human T cell lymphotropic virus type I. Aim: To describe the clinical and laboratory features of 26 caucasian chilean patients, with HTLV-I positive adult T-cell leukemia lymphoma (ATLL). Material and methods: Diagnostic criteria included clinical features, cell morphology, immunophenotype, HTLV-I serology and/or DNA analysis by southern blot or PCR. Results: According to the clinical presentation, 12 cases had the acute ATLL form, 6 had a lymphoma, 4 the chronic form and 4 had smoldering ATLL. The median presentation age was 50 years, younger than the Japanese patients, but significantly older than patients from other south american countries (eg Brasil, Jamaica, Colombia). The main clinical features: lymphadenopathy, skin lesions and hepatosplenomegaly, were similar in frequency to those of patients from other countries, except for the high incidence of associated neurological disease. Tropical spastic paraparesis (TSP) in our series of ATLL, was seen in one third of the patients (8/26). A T-cell immunophenotype was shown in all 26 cases and HTLV-I serology was positive in 25/26 patients. Molecular analysis on the seronegative patient showed clonal integration of proviral HTLV-I DNA into the lymphocytes DNA, and thus he may have been a poor responder to the retroviral infection. Proviral DNA integration was also demonstrated in 15/16 patients being clonal in 10, polyclonal in 3 (all smoldering cases) and oligoclonal in one. Conclusions: ATLL in Chile has similar clinical and laboratory features than the disease in other parts of the world, except for a younger age than japanese patients but older than those from other latin american countries and a high incidence of patients with associated TSP. Detailed morphological and immunophenotypic analysis of the abnormal circulating lymphocytes, together with the documentation of HTLV-I by serology and/or DNA analysis are key tests for the identification of this disease

A study of adult T-cell leukemia/lymphoma incidence in central Brooklyn

Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in-patient beds in the catchment area, approximately 83 percent were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted.(Au)

A study of adult T-cell leukemia/lymphoma incidence in central Brooklyn.

Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in-patient beds in the catchment area, approximately 83% were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted.

[Adult T cell leukemia lymphoma in Chile. A clinical pathologic and molecular study of 26 patients]. / Leucemia linfoma T del adulto en Chile. Estudio clínico-patológico y molecular de 26 pacientes.

BACKGROUND: Adult T cell leukemia lymphoma is a lymphoproliferative syndrome etiologically associated to human T cell lymphotropic virus type I. AIM: To describe the clinical and laboratory features of 26 Caucasian Chilean patients, with HTLV-I positive adult T-cell leukemia lymphoma (ATLL). MATERIAL AND METHODS: Diagnostic criteria included clinical features, cell morphology, immunophenotype, HTLV-I serology and/or DNA analysis by Southern blot or PCR. RESULTS: According to the clinical presentation, 12 cases had the acute ATLL form, 6 had a lymphoma, 4 the chronic form and 4 had smoldering ATLL. The median presentation age was 50 years, younger than the Japanese patients, but significantly older than patients from other South American countries (e.g. Brasil, Jamaica, Colombia). The main clinical features: lymphadenopathy, skin lesions and hepatosplenomegaly, were similar in frequency to those of patients from other countries, except for the high incidence of associated neurological disease. Tropical Spastic Paraparesis (TSP) in our series of ATLL, was seen in one third of the patients (8/26). A T-cell immunophenotype was shown in all 26 cases and HTLV-I serology was positive in 25/26 patients. Molecular analysis on the seronegative patient showed clonal integration of proviral HTLV-I DNA into the lymphocytes DNA, and thus he may have been a poor responder to the retroviral infection. Proviral DNA integration was also demonstrated in 15/16 patients being clonal in 10, polyclonal in 3 (all smoldering cases) and oligoclonal in one. CONCLUSIONS: ATLL in Chile has similar clinical and laboratory features than the disease in other parts of the world, except for a younger age than Japanese patients but older than those from other Latin American countries and a high incidence of patients with associated TSP. Detailed morphological and immunophenotypic analysis of the abnormal circulating lymphocytes, together with the documentation of HTLV-I by serology and/or DNA analysis are key tests for the identification of this disease.

Mecanismos de ativaçäo do linfócito T e induçäo da leucemia linfoma T do adulto pelo HTLV I / Lymphocyte T activation and adult T lymphoma-leukemia induction by HTLV I

A infecçäo pelo vírus linfotrópico de célula T, tipo I (HTLV I), endêmica em algumas regiöes do mundo, ganha conotaçäo principalmente pelo fato de induzir a leucemia linfoma T do adulto e paraparesia espástica tropical/mielopatia associada ao HTLV I. O conhecimento da fisiopatologia da transformaçäo da célula T auxilia tanto a compreensäo das vias normais de ativaçäo/proliferaçäo do linfócito, como no mecanismo de aparecimento de doenças linfoproliferativas. As estratégias usadas pelo vírus para induzir à proliferaçäo celular afeta o ciclo celular em diferentes estágios e em diferentes vias de sinalizaçäo. Seräo analisadas as principais vias envolvidas nessa questäo e alguns mecanismos de açäo do vírus.

Clinical and laboratory features of adult T-cell leukaemia lymphoma in Barbados.

We describe the clinical and pathological features of 23 Afro-Caribbean patients with adult T-cell leukaemia/lymphoma admitted to the Queen Elizabeth Hospital, Barbados over a 5 year period. There were 9 males and 14 females, with a median age of 38 years (range 14-84). Twelve had acute leukaemia, 10 lymphoma (including 4 with solitary extra nodal lesions) and 1 smouldering subtype. Two patients had a past history of tropical spastic paraparesis/HTLV I associated myelopathy (TSP/HAM). The prognosis was poor, with only 3 complete responses to chemotherapy (CHOP) lasting from 9 to 36 months. We conclude that ATLL in Barbados is similar to the disease in the other Caribbean islands and Japan, except that in Barbados the age of onset is over a decade younger than in Japan.

Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis, and adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) and human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are associated with differing patterns of immune dysfunction. Biomarkers of immune activation may correlate with perturbations of immune function associated with these diseases. We conducted a pilot cross-sectional study to assess four candidate biomarkers of immune activation. beta 2-microglobulin, neopterin, tryptophan, and kynurenine levels were assayed in stored sera from asymptomatic, human T-cell leukemia virus type I (HTL V-I)-seronegative (HTLV-I-) and HTLV-I-seropositive (HTLV-I+) individuals, and ATL and HAM/TSP patients previously enrolled in seroepidemiological studies in Jamaica. Mean levels of beta 2-microglobulin, neopterin, and kynurenine were significantly elevated among ATL patients compared to the other study groups. Mean tryptophan levels were significantly lower among ATL and HAM/TSP patients than HTLV-I- and HTLV-I+ groups. No significant differences in biomarkers were found between the HTLV-I- and HTLV-I+ groups. Among HAM/TSP patients, a significant association was found between elevated neopterin levels and symptoms of less than 4 years duration. In Cox proportional hazards regression modeling, neopterin and tryptophan were found to be independent predictors of survival among ATL patients. This study demonstrates a differential pattern of biomarkers of immune activation among ATL and HAM/TSP patients compared to HTLV-I- and HTLV-I+ individuals. Neopterin and tryptophan may be useful clinical indicators of disease severity and prognosis among HAM/TSP and ATL patients.