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 Citations (Scopus)

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

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Cercocebus atys
Interleukin-7
T-cells
Cercocebus
T-Lymphocytes
Macaca
HIV Infections
Simian Acquired Immunodeficiency Syndrome
Infection
Simian Immunodeficiency Virus
Viremia
Opportunistic Infections
Cell proliferation
Viruses
Maintenance
Cell Proliferation
Cytokines
Plasmas

ASJC Scopus subject areas

  • Hematology

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Timely triggering of homeostatic mechanisms involved in the regulation of T-cell levels in SIVsm-infected sooty mangabeys. / Muthukumar, Alagarraju; Zhou, Dejiang; Paiardini, Mirko; Barry, Ashley P.; Cole, Kelly S.; McClure, Harold M.; Staprans, Silvija I.; Silvestri, Guido; Sodora, Donald L.

In: Blood, Vol. 106, No. 12, 01.12.2005, p. 3839-3845.

Research output: Contribution to journalArticle

Muthukumar, A, Zhou, D, Paiardini, M, Barry, AP, Cole, KS, McClure, HM, Staprans, SI, Silvestri, G & Sodora, DL 2005, 'Timely triggering of homeostatic mechanisms involved in the regulation of T-cell levels in SIVsm-infected sooty mangabeys', Blood, vol. 106, no. 12, pp. 3839-3845. https://doi.org/10.1182/blood-2005-01-0394
Muthukumar, Alagarraju ; Zhou, Dejiang ; Paiardini, Mirko ; Barry, Ashley P. ; Cole, Kelly S. ; McClure, Harold M. ; Staprans, Silvija I. ; Silvestri, Guido ; Sodora, Donald L. / Timely triggering of homeostatic mechanisms involved in the regulation of T-cell levels in SIVsm-infected sooty mangabeys. In: Blood. 2005 ; Vol. 106, No. 12. pp. 3839-3845.
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