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 nonhuman 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 repli cation, where CD4(+) T-cell destruction is chronic.

Original languageEnglish (US)
Pages (from-to)748-58
Number of pages11
JournalBlood
Volume116
Issue number5
DOIs
StatePublished - Aug 5 2010

Keywords

  • Animals
  • Antibodies, Monoclonal/pharmacology
  • CD4-Positive T-Lymphocytes/cytology
  • CD8-Positive T-Lymphocytes/cytology
  • Cell Division
  • Cell Lineage
  • Cercocebus atys/immunology
  • Homeostasis/immunology
  • Immunity, Innate
  • Interleukin-15/blood
  • Interleukin-7/blood
  • Lymphocyte Activation
  • Lymphocyte Depletion
  • Macaca mulatta/immunology
  • Simian Acquired Immunodeficiency Syndrome/genetics
  • Species Specificity
  • T-Lymphocyte Subsets/cytology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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