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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.
- Authors
Lishomwa C.6Ndhlovu; 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.
- 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-32 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.
- Subjects
HTLV-I; HIV-positive persons; T cells; IMMUNOGLOBULINS; MUCINS; PARAPARESIS; VIRAL replication; PATHOGENIC microorganisms; NEUROLOGY
- Publication
PLoS Neglected Tropical Diseases, 2011, Vol 5, Issue 4, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0001030