Lineage-specific T-cell reconstitution following in vivo CD4+ and CD8+ lymphocyte depletion in nonhuman primates

Jessica C. Engram, Barbara Cervasi, Jose A.M. Borghans, Nichole R. Klatt, Shari N. Gordon, Ann Chahroudi, James G. Else, Robert S. Mittler, Donald L. Sodora, Rob J. De Boer, Jason M. Brenchley, Guido Silvestri, Mirko Paiardini

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Many features of T-cell homeostasis in primates are still unclear, thus limiting our understanding of AIDS pathogenesis, in which T-cell homeostasis is lost. Here, we performed experiments of in vivo CD4+ or CD8 + lymphocyte depletion in 2 non-human primate species, rhesus macaques (RMs) and sooty mangabeys (SMs). Whereas RMs develop AIDS after infection with simian immunodeficiency virus (SIV), SIV-infected SMs are typically AIDS-resistant. We found that, in both species, most CD4+ or CD8+ T cells in blood and lymph nodes were depleted after treatment with their respective antibodies. These CD4+ and CD8 + lymphocyte depletions were followed by a largely lineage-specific CD4+ and CD8+ T-cell proliferation, involving mainly memory T cells, which correlated with interleukin-7 plasma levels. Interestingly, SMs showed a faster repopulation of naive CD4+ T cells than RMs. In addition, in both species CD8+ T-cell repopulation was faster than that of CD4+ T cells, with CD8+ T cells reconstituting a normal pool within 60 days and CD4+ T cells remaining below baseline levels up to day 180 after depletion. While this study revealed subtle differences in CD4+ T-cell repopulation in an AIDS-sensitive versus an AIDS-resistant species, such differences may have particular relevance in the presence of active SIV replication, where CD4 + T-cell destruction is chronic.

Original languageEnglish (US)
Pages (from-to)748-758
Number of pages11
JournalBlood
Volume116
Issue number5
DOIs
StatePublished - Aug 5 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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