Rapid down-regulation of γc on T cells in early SIV infection correlates with impairment of T-cell function

FASEB J. 2012 Jun;26(6):2294-305. doi: 10.1096/fj.11-195180. Epub 2012 Feb 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Cytokines / blood
  • Down-Regulation
  • Interleukin Receptor Common gamma Subunit / biosynthesis*
  • Interleukin-15 / pharmacology
  • Interleukin-2 / pharmacology
  • Interleukin-7 / pharmacology
  • Macaca mulatta
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / physiopathology
  • T-Lymphocytes / physiology*


  • Cytokines
  • Interleukin Receptor Common gamma Subunit
  • Interleukin-15
  • Interleukin-2
  • Interleukin-7