HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation

Anjana Yadav, Shibani Pati, Anhthu Nyugen, Oxana Barabitskaja, Prosanta Mondal, Michael Anderson, Robert C. Gallo, David L. Huso, William Reid

Research output: Contribution to journalArticlepeer-review

Abstract

Impaired CD4+ T cell responses, resulting in dysregulated T-helper 1 (Th1) effector and memory responses, are a common result of HIV-1 infection. These defects are often preceded by decreased expression and function of the α/β T cell receptor (TCR)-CD3 complex and of co-stimulatory molecules including CD28, resulting in altered T cell proliferation, cytokine secretion and cell survival. We have previously shown that HIV Tg rats have defective development of T cell effector function and generation of specific effector/memory T cell subsets. Here we identify abnormalities in activated HIV-1 Tg rat CD4+ T cells that include decreased pY505 dephosphorylation of Lck (required for Lck activation), decreased CD28 function, reduced expression of the anti-apoptotic molecule Bcl-xL, decreased secretion of the mitogenic lympokine interleukin-2 (IL-2) and increased activation induced apoptosis. These events likely lead to defects in antigen-specific signaling and may help explain the disruption of Th1 responses and the generation of specific effector/memory subsets in transgenic CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)357-365
Number of pages9
JournalVirology
Volume353
Issue number2
DOIs
StatePublished - Sep 30 2006

Keywords

  • CD28
  • HIV-1
  • Lck
  • Memory
  • Transgenic

ASJC Scopus subject areas

  • Virology

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