AEGiS-9CROI: Dynamics of T-Lymphocyte Turnover in Sooty Mangabeys, a Nonpathogenic Host of Simian Immunodeficiency Virus Infection

9th Conference on Retroviruses and Opportunistic Infections

Seattle, Washington - February 24 -February 28, 2002

Dynamics of T-Lymphocyte Turnover in Sooty Mangabeys, a Nonpathogenic Host of Simian Immunodeficiency Virus Infection

Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 22
Kaur A, Barabasz AF, Rosenzweig M, McClure H, Feinberg MB, Johnson RP; New England Regional Primate Res. Ctr., Harvard Med. Sch., Southborough, MA

BACKGROUND: Although several studies have demonstrated the presence of increased T- lymphocyte turnover in pathogenic HIV/SIV infection, there is little data in nonpathogenic lentiviral infection. Sooty mangabeys, a natural host of SIV, do not develop AIDS despite high viral loads and viral turnover rates that are comparable to those observed in pathogenic SIV infection.

METHODS: We investigated lymphocyte turnover in sooty mangabeys using the nucleoside analog bromodeoxyuridine (BrdU) to label dividing cells in vivo. 5 SIV-negative and 6 naturally SIV-infected sooty mangabeys were administered 60 mg/kg BrdU daily for 14 days via the intraperitoneal route. Labeling of lymphocytes in peripheral blood with BrdU was monitored using 5-color flow cytometry during the labeling phase and for 60-90 days during the BrdU washout phase.

RESULTS: BrdU-labeled cells accumulated at a linear rate and declined exponentially. At the end of the labeling phase, the mean peak values for BrdU-labeled lymphocytes were not significantly different in normal and SIV-infected sooty mangabeys for CD3+8+ T lymphocytes (8.2% vs 11.1%); for CD4⁺ T lymphocytes (14.1% vs 15.4%); or for CD20+ B lymphocytes (18.7% vs 20.6%). The rates of uptake of BrdU (as analyzed by linear regression) and the rates of decay of BrdU label (as determined by exponential regression analysis) were also comparable for CD4⁺ and CD8+ T lymphocytes, and for B lymphocytes in SIV-negative and SIV-infected sooty mangabeys. In both normal and SIV-infected mangabeys, the rates of uptake and decay of BrdU in CD4⁺ T lymphocytes were closely correlated with those of CD8+ T lymphocytes (R value >0.95). As previously observed in rhesus macaques, memory phenotype (CD45RA(-)62L(-)) T lymphocytes had increased rates of turnover compared with naïve (CD45RA(+)62L(+ )) T lymphocytes in both normal and SIV-infected mangabeys.

CONCLUSION: Despite viral loads of up to 10(7) copies/mL, turnover of CD4⁺ and CD8+ T cells is not increased in SIV-infected sooty mangabeys. These findings, which contrast with the 3- to 5-fold increase in lymphocyte turnover observed in SIV-infected macaques and HIV-infected people, suggest that the absence of mechanisms that drive increased lymphocyte proliferation and death in pathogenic lentiviral infection may be a factor preventing CD4⁺ T lymphocyte depletion in non-pathogenic hosts of SIV.

Keywords: Cercocebus atys, SIV, CD8-Positive T-Lymphocytes, CD4-Positive T-Lymphocytes, Cercocebus, Macaca mulatta, Antigens, CD45, Antigens, CD4, Viral Load, Flow Cytometry, Animal, immunology

020224
22

Copyright © 2002 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.