Relative resistance in the development of T cell anergy in CD4+ T cells from simian immunodeficiency virus disease-resistant sooty mangabeys

P. Bostik, A. E. Mayne, F. Villinger, K. P. Greenberg, J. D. Powell, A. A. Ansari

Research output: Contribution to journalArticle

Abstract

Despite high viral loads, T cells from sooty mangabey (SM) monkeys that are naturally infected with SIV but remain clinically asymptomatic, proliferate and demonstrate normal Ag-specific memory recall CD4+ T cell responses. In contrast, CD4+ T cells from rhesus macaques (RM) experimentally infected with SIV lose Ag-specific memory recall responses and develop immunological anergy. To elucidate the mechanisms for these distinct outcomes of lentiviral infection, highly enriched alloreactive CD4+ T cells from humans, RM, and SM were anergized by TCR-only stimulation (signal 1 alone) and subsequently challenged with anti-CD3/anti-CD28 Abs (signals 1 + 2). Whereas alloreactive CD4+ T cells from humans and RM became anergized, surprisingly, CD4+ T cells from SM showed marked proliferation and IL-2 synthesis after restimulation. This resistance to undergo anergy was not secondary to a global deficiency in anergy induction of CD4+ T cells from SM since incubation of CD4+ T cells with anti-CD3 alone in the presence of rapamycin readily induced anergy in these cells. The resistance to undergo anergy was reasoned to be due to the ability of CD4+ T cells from SM to synthesize IL-2 when incubated with anti-CD3 alone. Analysis of phosphorylated kinases involved in T cell activation showed that the activation of CD4+ T cells by signal 1 in SM elicited a pattern of response that required both signals 1 + 2 in humans and RM. This function of CD4+ T cells from SM may contribute to the resistance of this species to SIV-induced disease.

Original languageEnglish (US)
Pages (from-to)506-516
Number of pages11
JournalJournal of Immunology
Volume166
Issue number1
DOIs
StatePublished - Jan 1 2001

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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