Naive T cells are dispensable for memory CD4 + T cell homeostasis in progressive simian immunodeficiency virus infection

Afam A. Okoye, Mukta Rohankhedkar, Chike Abana, Audrie Pattenn, Matthew Reyes, Christopher Pexton, Richard Lum, Andrew Sylwester, Shannon L. Planer, Alfred Legasse, Byung S. Park, Michael Piatak, Jeffrey D. Lifson, Michael K. Axthelm, Louis J. Picker

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The development of AIDS in chronic HIV/simian immunodeficiency virus (SIV) infection has been closely linked to progressive failure of CD4 + memory T cell (T M) homeostasis. CD4+ naive T cells (T N) also decline in these infections, but their contribution to disease progression is less clear. We assessed the role of CD4 + T N in SIV pathogenesis using rhesus macaques (RM s) selectively and permanently depleted of CD4 + T N before SIV infection. CD4 + T N-depleted and CD4 + T N-repleted RMs were created by subjecting juvenile RMs to thymectomy versus sham surgery, respectively, followed by total CD4 + T cell depletion and recovery from this depletion. Although thymectomized and sham-treated RMs manifested comparable CD4 + T M recovery, only sham-treated RMs reconstituted CD4 + T N. CD4 + T N-depleted RMs responded to SIVmac239 infection with markedly attenuated SIV-specific CD4 + T cell responses, delayed SIVenv-specific Ab responses, and reduced SIV-specific CD8 + T cell responses. However, CD4 + T N-depleted and -repleted groups showed similar levels of SIV replication. Moreover, CD4 + T N deficiency had no significant effect on CD4 + T M homeostasis (either on or off anti-retroviral therapy) or disease progression. These data demonstrate that the CD4 + T N compartment is dispensable for CD4 + T M homeostasis in progressive SIV infection, and they confirm that CD4 + T M comprise a homeostatically independent compartment that is intrinsically capable of self-renewal.

Original languageEnglish (US)
Pages (from-to)641-651
Number of pages11
JournalJournal of Experimental Medicine
Volume209
Issue number4
DOIs
StatePublished - Apr 9 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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