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

Blood. 2005 Dec 1;106(12):3839-45. doi: 10.1182/blood-2005-01-0394. Epub 2005 Aug 16.

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/microL) 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/microL) 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.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology*
  • Cercocebus atys
  • Flow Cytometry
  • Homeostasis / immunology
  • Interleukin-15 / blood
  • Interleukin-7 / blood*
  • Interleukin-7 / immunology
  • Monkey Diseases / blood
  • Monkey Diseases / immunology*
  • Monkey Diseases / virology*
  • Simian Immunodeficiency Virus / immunology*
  • Time Factors
  • Viral Load

Substances

  • Interleukin-15
  • Interleukin-7