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

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 5, n. 4, p. 9-pg., 2011-04-01.

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. (AU)

• FAPESP's process: 10/05845-0 - Cellular immune responses in infectious diseases and primary immunodeficiencies
• Grantee: Esper Georges Kallás
• Support Opportunities: Research Grants - Visiting Researcher Grant - International