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- Title
Rapid down-regulation of γ<sub>c</sub> on T cells in early SIV infection correlates with impairment of T-cell function.
- Authors
Huanbin Xu; Xiaolei Wang; Pahar, Bapi; Alvarez, Xavier; Rasmussen, Kelsi K.; Lackner, Andrew A.; Veazey, Ronald S.
- Abstract
The common γc subunit molecule is shared among all γc 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 γc on T cells during SIV infection in Rhesus macaques. Surface γc 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 γc expression was rapidly and significantly down-regulated on T cells in acute infection with patho- genic 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 γc+ CD8+ T cells in individual tissues. γc+ T cells were mainly functional as evidenced by higher cytokine secretion and proliferative capacity. Further in vitro experiments found that surface γc expression could be down-regulated following high level of IL-7 treatment by both internalization and shedding. Down-regulation of γc 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.
- Subjects
CYTOKINES; CD4 antigen; T cells; SIMIAN immunodeficiency virus; HIV; IMMUNOLOGY
- Publication
FASEB Journal, 2012, Vol 26, Issue 6, p2294
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.11-195180