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

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.

• Authors: Alagarraju Muthukumar, Dejiang Zhou, Mirko Paiardini, Ashley P Barry, Kelly S Cole, Harold M McClure, Silvija I Staprans, Guido Silvestri, Donald L Sodora
• Journal: Blood (Blood) Vol. 106 Issue 12 Pg. 3839-45 (Dec 01 2005) ISSN: 0006-4971 [Print] United States
• PMID: 16105985 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Interleukin-15
• Interleukin-7

Topics

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