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 Vol. 5; no. 4; p. e1030
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2011; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Asymptomatic; CD8-Positive T-Lymphocytes - immunology; Cells; Cytokines; Disease; Female; Gene Expression Profiling; Gene Products, tax - immunology; Hepatitis A Virus Cellular Receptor 2; Human T-lymphotropic virus 1 - immunology; Humans; Immunoglobulins; Infections; Lymphocytes; Male; Medicine; Membrane Proteins - biosynthesis; Middle Aged; Paraparesis, Tropical Spastic - immunology; Paraparesis, Tropical Spastic - pathology; Proteins; Spasticity; Tropical diseases; Vaccines; Viral infections; CD8-Positive T-Lymphocytes; Membrane Proteins; Paraparesis, Tropical Spastic; Humans; Middle Aged; Gene Products, tax; Adult; Female; Male; Aged; Gene Expression Profiling; Human T-lymphotropic virus 1
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0001030

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.