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

• Published in: PLoS Neglected Tropical Diseases
• Main Authors: 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
• Format: Article in Journal/Newspaper
• Language: English
• Published: Public Library of Science (PLoS) 2011
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Public aspects of medicine; RA1-1270; Arctic
• Online Access: https://doi.org/10.1371/journal.pntd.0001030; https://doaj.org/article/190061c58fcc422885cc5232b6d96652

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.