Timely triggering of homeostatic mechanisms involved in the regulation of T-cell levels in SIVsm-infected sooty mangabeys

Alagarraju Muthukumar, Dejiang Zhou, Mirko Paiardini, Ashley P. Barry, Kelly S. Cole, Harold M. McClure, Silvija I. Staprans, Guido Silvestri, Donald L. Sodora

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Sooty mangabeys, the natural host of simian immunodeficiency virus (SIVsm), generally avoid progressive depletion of CD4+ T cells and opportunistic infections associated with infection of humans (HIV) and macaques (SIVmac). The means by which the SIVsm-infected mangabeys maintain CD4 + T-cell levels despite high rates of viral replication is unknown. One cytokine that has a key role in the regulation of T-cell levels is interleukin-7 (IL-7). Here, the longitudinal assessment of 6 SIVsm-infected mangabeys identified an early increase in plasma IL-7 levels at weeks 1 to 5 after infection. This IL-7 increase correlated with an early decline in CD4 + T-cell levels (decline of 492-1171 cells/μL) accompanying acute viremia. Elevated IL-7 levels were followed by increased T-cell proliferation (Ki67) and maintenance of lower but stable (more than 500 cells/μL) CD4 + T-cell levels in each mangabey through 37 weeks of infection. These data contrast with our earlier studies in SIVmac-infected macaques, in which the IL-7 increase was delayed until 20 to 40 weeks after infection, just before the onset of simian AIDS. Taken together, these data suggest that timely triggering of IL-7 is important for stabilizing healthy T-cell levels in mangabeys and that timely administration of exogenous IL-7 may show benefit during pathogenic SIVmac and HIV infection.

Original languageEnglish (US)
Pages (from-to)3839-3845
Number of pages7
JournalBlood
Volume106
Issue number12
DOIs
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Muthukumar, A., Zhou, D., Paiardini, M., Barry, A. P., Cole, K. S., McClure, H. M., Staprans, S. I., Silvestri, G., & Sodora, D. L. (2005). Timely triggering of homeostatic mechanisms involved in the regulation of T-cell levels in SIVsm-infected sooty mangabeys. Blood, 106(12), 3839-3845. https://doi.org/10.1182/blood-2005-01-0394