Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection

Jacob D. Estes, Qingsheng Li, Matthew R. Reynolds, Stephen Wietgrefe, Lijie Duan, Timothy Schacker, Louis J. Picker, David I. Watkins, Jeffrey D. Lifson, Cavan Reilly, John Carlis, Ashley T. Haase

Research output: Contribution to journalArticlepeer-review

208 Scopus citations


Here we report the results of an investigation into the possibility that one mechanism responsible for the establishment of persistent human immunodeficiency virus infection is an early regulatory T (Treg) cell response that blunts virus-specific responses. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model, we show that, indeed, viral replication and immune activation in lymphatic tissue drive a premature immunosuppressive response, with dramatic increases in the frequencies of CD4+CD25+FOXP3+ Treg cells, transforming growth factor-β1+ cells, interleukin-10+ cells, and indoleamine 2,3-dioxygenase+CD3+ cells. When we compared SIV infection with rhesus cytomegalovirus (RhCMV) infection, we found that the frequency of Treg cells paralleled the magnitude of immune activation during both infections but that the magnitude of immune activation and of the Treg cell response were lower and peaked much later during RhCMV infection. Importantly, the frequency of Treg cells inversely correlated with the magnitude of the SIV-specific cytotoxic T lymphocyte response. We conclude that an early Treg cell response during acute SIV infection may contribute to viral persistence by prematurely limiting the antiviral immune response before infection is cleared.

Original languageEnglish (US)
Pages (from-to)703-712
Number of pages10
JournalJournal of Infectious Diseases
Issue number5
StatePublished - Mar 1 2006

Bibliographical note

Funding Information:
Financial support: National Institutes of Health (grants R01 AI48484 and AI056997 to A.T.H.; grant T32 AI07421 to J.D.E.; grant U51 RR00169 to the California National Primate Research Center; grants R01 AI51239 and R01 AI51596 to C.J.M.; and grant P51 RR00167 to the Wisconsin National Primate Research Center); National Cancer Institute (contract NO1-CO-124000 to J.D.L.).


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