HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: Implications for progression to neurological complications

Lishomwa C. Ndhlovu; Fabio E. Leal; Aaron M. Hasenkrug; Aashish R. Jha; Karina I. Carvalho; Ijeoma G. Eccles-James; Fernanda R. Bruno; Raphaella G.S. Vieira; Vanessa A. York; Glen M. Chew; R. Brad Jones; Yuetsu Tanaka; Walter K. Neto; Sabri S. Sanabani; Mario A. Ostrowski; Aluisio C. Segurado; Douglas F. Nixon; Esper G. Kallas

doi:10.1371/journal.pntd.0001030

HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: Implications for progression to neurological complications

Lishomwa C. Ndhlovu, Fabio E. Leal, Aaron M. Hasenkrug, Aashish R. Jha, Karina I. Carvalho, Ijeoma G. Eccles-James, Fernanda R. Bruno, Raphaella G.S. Vieira, Vanessa A. York, Glen M. Chew, R. Brad Jones, Yuetsu Tanaka, Walter K. Neto, Sabri S. Sanabani, Mario A. Ostrowski, Aluisio C. Segurado, Douglas F. Nixon, Esper G. Kallas

Biology

Research output: Contribution to journal › Article › peer-review

Abstract

The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially "exhausted" and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis), we investigated the expression of the Tim-3 receptor on CD8⁺ T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8⁺ and CD4⁺ T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8⁺ T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3⁺ and Tim-3^- fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications.

Original language	English (US)
Article number	e1030
Journal	PLoS neglected tropical diseases
Volume	5
Issue number	4
DOIs	https://doi.org/10.1371/journal.pntd.0001030
State	Published - Apr 2011

ASJC Scopus subject areas

Public Health, Environmental and Occupational Health
Infectious Diseases

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Ndhlovu, L. C., Leal, F. E., Hasenkrug, A. M., Jha, A. R., Carvalho, K. I., Eccles-James, I. G., Bruno, F. R., Vieira, R. G. S., York, V. A., Chew, G. M., Jones, R. B., Tanaka, Y., Neto, W. K., Sanabani, S. S., Ostrowski, M. A., Segurado, A. C., Nixon, D. F., & Kallas, E. G. (2011). HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: Implications for progression to neurological complications. PLoS neglected tropical diseases, 5(4), Article e1030. https://doi.org/10.1371/journal.pntd.0001030

Ndhlovu, LC, Leal, FE, Hasenkrug, AM, Jha, AR, Carvalho, KI, Eccles-James, IG, Bruno, FR, Vieira, RGS, York, VA, Chew, GM, Jones, RB, Tanaka, Y, Neto, WK, Sanabani, SS, Ostrowski, MA, Segurado, AC, Nixon, DF & Kallas, EG 2011, 'HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: Implications for progression to neurological complications', PLoS neglected tropical diseases, vol. 5, no. 4, e1030. https://doi.org/10.1371/journal.pntd.0001030

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title = "HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: Implications for progression to neurological complications",

abstract = "The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially {"}exhausted{"} and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis), we investigated the expression of the Tim-3 receptor on CD8+ T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8+ and CD4+ T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8+ T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3+ and Tim-3- fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications.",

author = "Ndhlovu, {Lishomwa C.} and Leal, {Fabio E.} and Hasenkrug, {Aaron M.} and Jha, {Aashish R.} and Carvalho, {Karina I.} and Eccles-James, {Ijeoma G.} and Bruno, {Fernanda R.} and Vieira, {Raphaella G.S.} and York, {Vanessa A.} and Chew, {Glen M.} and Jones, {R. Brad} and Yuetsu Tanaka and Neto, {Walter K.} and Sanabani, {Sabri S.} and Ostrowski, {Mario A.} and Segurado, {Aluisio C.} and Nixon, {Douglas F.} and Kallas, {Esper G.}",

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AU - Ndhlovu, Lishomwa C.

AU - Leal, Fabio E.

AU - Hasenkrug, Aaron M.

AU - Jha, Aashish R.

AU - Carvalho, Karina I.

AU - Eccles-James, Ijeoma G.

AU - Bruno, Fernanda R.

AU - Vieira, Raphaella G.S.

AU - York, Vanessa A.

AU - Chew, Glen M.

AU - Jones, R. Brad

AU - Tanaka, Yuetsu

AU - Neto, Walter K.

AU - Sanabani, Sabri S.

AU - Ostrowski, Mario A.

AU - Segurado, Aluisio C.

AU - Nixon, Douglas F.

AU - Kallas, Esper G.

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AB - The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially "exhausted" and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis), we investigated the expression of the Tim-3 receptor on CD8+ T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8+ and CD4+ T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8+ T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3+ and Tim-3- fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications.

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HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: Implications for progression to neurological complications

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