title: HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: implications for progression to neurological complications.
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.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America. lndhlovu@medsfgh.ucsf.edu
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.forename: Fabio E
authors.initials: FE
authors.lastname: Leal
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Hasenkrug
authors.forename: Aashish R
authors.initials: AR
authors.lastname: Jha
authors.forename: Karina I
authors.initials: KI
authors.lastname: Carvalho
authors.forename: Ijeoma G
authors.initials: IG
authors.lastname: Eccles-James
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Bruno
authors.forename: Raphaella G S
authors.initials: RG
authors.lastname: Vieira
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: York
authors.forename: Glen M
authors.initials: GM
authors.lastname: Chew
authors.forename: R Brad
authors.initials: RB
authors.lastname: Jones
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Walter K
authors.initials: WK
authors.lastname: Neto
authors.forename: Sabri S
authors.initials: SS
authors.lastname: Sanabani
authors.forename: Mario A
authors.initials: MA
authors.lastname: Ostrowski
authors.forename: Aluisio C
authors.initials: AC
authors.lastname: Segurado
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D016356:Gene Products, tax / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000473:pathology*
chemical_list: D016356:Gene Products, tax; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; C514970:tax protein, Human T-lymphotrophic virus 1