HTLV-1 Tax Specific CD8+ T Cells Express Low Levels of Tim-3 in HTLV-1 Infection: Implications for Progression to Neurological Complications

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.

National Institutes of Health (NIH), University of California, San Francisco-Gladstone Institute of Virology & Immunology Center[P30 AI027763]

STD

AIDS, Ministry of Health[914/BRA/3014 - UNESCO/Kallas]

Sao Paulo City Health Department[2004-0.168.922-7/Kallas]

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[04/ 15856-9/Kallas]

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[2010/05845-0/Kallas and Nixon]

(NIH) John E. Fogarty International Center[D43 TW00003]

National Institute of Allergy and Infectious Diseases (LCN)[R56AI083112]

Montana State Complex Biological Systems Research

Howard Hughes Medical Institute