title: Rapid down-regulation of γc on T cells in early SIV infection correlates with impairment of T-cell function.
abstract: The common γ(c) subunit molecule is shared among all γ(c) cytokines and clearly involved in T-cell function, but its role in HIV infection and immunity is not well understood. Here, we examined expression and function of γ(c) on T cells during SIV infection in Rhesus macaques. Surface γ(c) distribution was differentially expressed on CD4(+) and CD8(+) T cells, and CD4(+) naive/memory cell populations in various lymphoid tissues of normal macaques. However, surface γ(c) expression was rapidly and significantly down-regulated on T cells in acute infection with pathogenic SIV, compared to infection with a less virulent SHIV or controls and did not recover on CD8(+) T cells in the chronic stage. Moreover, the peripheral and CD4(+)T cell loss was inversely correlated with γ(c)(+) CD8(+) T cells in individual tissues. γ(c)(+) T cells were mainly functional as evidenced by higher cytokine secretion and proliferative capacity. Further in vitro experiments found that surface γ(c) expression could be down-regulated following high level of IL-7 treatment by both internalization and shedding. Down-regulation of γ(c) during early HIV/SIV infection may inhibit T-cell function, particularly of CD8(+) T cells, and, may be linked with immune failure and loss of viral containment.
authors.affiliation: Tulane National Primate Research Center, Division of Comparative Pathology, 18703 Three Rivers Rd., Covington, LA 70433, USA.
authors.forename: Huanbin
authors.initials: H
authors.lastname: Xu
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.forename: Bapi
authors.initials: B
authors.lastname: Pahar
authors.forename: Xavier
authors.initials: X
authors.lastname: Alvarez
authors.forename: Kelsi K
authors.initials: KK
authors.lastname: Rasmussen
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation; D053631:Interleukin Receptor Common gamma Subunit / Q000096:biosynthesis*; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D016207:Cytokines; D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7