Memory lineage relationships in HTLV-1-specific CD8+ cytotoxic T cells

Johnson-Nauroth, Julie M.; Graber, Jerome; Yao, Karen; Jacobson, Steve; Calabresi, Peter A.

doi:10.1016/j.jneuroim.2006.03.013

Cited by 13 publications

(12 citation statements)

References 50 publications

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“…3). This is contradictory to another study (58), which reported rapid ex vivo expansion of effector memory T cells in PBMCs of HAM/TSP patients in response to Tax. It is important to note that this study cultured the T cells for a longer duration compared to short 6 h stimulation in our study.…”

Section: Discussioncontrasting

confidence: 97%

Lack of Recall Response to Tax in ATL and HAM/TSP Patients But Not in Asymptomatic Carriers of Human T-cell Leukemia Virus Type 1

et al. 2013

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The immunopathogenic mechanisms responsible for debilitating neurodegenerative and oncologic diseases associated with human T-cell leukemia virus type 1 (HTLV-1) are not fully understood. In this respect, a patient cohort from HTLV-1 endemic region that included seronegative controls (controls), asymptomatic carriers (ACs), and patients with adult T-cell leukemia (ATL) or HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was analyzed for CD8+ T cells functionality in response to the viral antigen Tax and a superantigen SEB. Overall, there was a poor recall response to Tax and less polyfunctionality in cells from ATL and HAM/TSP patients but not in ACs explaining why these cells remain ineffective in limiting viral burden and controlling disease progression. On the other hand, response to superantigen SEB was similar in all the groups, suggesting that the observed defects in CD8 + T cells are not generalized but rather HTLV-specific. As an underlying mechanism, programmed death-1 (PD-1) receptor was found to be highly unregulated in Tax-responsive cells from ATL and HAM/TSP but not from ACs and directly correlated with the lack of polyfunctionality in these individuals. Further, an opposite dynamic was observed between PD-1 and MIP-1α with proviral loads revealing new avenues of understanding the immunopathogenesis of human chronic viral infections. Additionally, we identified key cytokine signatures defining the immune activation status of clinical samples by the luminex analyses. Collectively, our findings suggest that reconstitution of fully functional CTLs, stimulation of MIP-1α expression, and/or blockade of the PD-1 pathway as potential approaches for immunotherapy and therapeutic vaccine against HTLV-mediated diseases.

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Section: Discussioncontrasting

confidence: 97%

Lack of Recall Response to Tax in ATL and HAM/TSP Patients But Not in Asymptomatic Carriers of Human T-cell Leukemia Virus Type 1

et al. 2013

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“…Indeed, we found a HTLV-2-specific CD8 ϩ T cell memory phenotype similar to that observed in HAM/TSP patients and in CMV infection, with high percentages of T EMRA cells (37,38). Whether this represents a particular differentiation phenotype associated with HTLV-2 infection or reflects a persistent activation and expansion of virus-specific CTLs remains to be determined.…”

Section: Discussionsupporting

confidence: 71%

High Frequencies of Functionally Competent Circulating Tax-Specific CD8+ T Cells in Human T Lymphotropic Virus Type 2 Infection

Oliveira

Hayakawa

Schor

et al. 2009

The Journal of Immunology

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Human T lymphotropic virus type 2 (HTLV-2) is characterized by a clinically asymptomatic persistent infection in the vast majority of infected individuals. In this study, we have characterized for the first time ex vivo specific CTL responses against the HTLV-2 Tax protein. We could detect CTL responses only against a single HLA-A*0201-restricted Tax2 epitope, comprising residues 11–19 (LLYGYPVYV), among three alleles screened. Virus-specific CTLs could be detected in most evaluated subjects, with frequencies as high as 24% of circulating CD8+ T cells. The frequency of specific CTLs had a statistically significant positive correlation with proviral load levels. The majority of virus-specific CD8+ T cells exhibited an effector memory/terminally differentiated phenotype, expressed high levels of cytotoxicity mediators, including perforin and granzyme B, and lysed in vitro target cells pulsed with Tax2(11–19) synthetic peptide in a dose-dependent manner. Our findings suggest that a strong, effective CTL response may control HTLV-2 viral burden and that this may be a significant factor in maintaining persistent infection and in the prevention of disease in infected individuals.

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“…In this study, we defined the memory phenotype of Tax-specific CD8 ϩ T cells from STLV-1-infected baboons based on the expression of CD45RA and the chemokine receptor CCR7 (50,51). To determine the memory phenotype of Tax-specific CD8 ϩ T cells, we stimulated PBMCs from 10 animals with their best-responding Tax peptide pool (usually pool 6 or 7) and assessed the expression of CD107a and cytokines.…”

Section: Cd8 ؉ T Cells From Several Stlv-1-infected Baboons Target Tamentioning

confidence: 99%

Cellular Immune Responses against Simian T-Lymphotropic Virus Type 1 Target Tax in Infected Baboons

Castro

Giret

Magnani

et al. 2016

J Virol

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Memory lineage relationships in HTLV-1-specific CD8+ cytotoxic T cells

Cited by 13 publications

References 50 publications

Lack of Recall Response to Tax in ATL and HAM/TSP Patients But Not in Asymptomatic Carriers of Human T-cell Leukemia Virus Type 1

Lack of Recall Response to Tax in ATL and HAM/TSP Patients But Not in Asymptomatic Carriers of Human T-cell Leukemia Virus Type 1

High Frequencies of Functionally Competent Circulating Tax-Specific CD8+ T Cells in Human T Lymphotropic Virus Type 2 Infection

Cellular Immune Responses against Simian T-Lymphotropic Virus Type 1 Target Tax in Infected Baboons

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