CD8+ cell depletion of SHIV89.6P-infected macaques induces CD4+ T cell proliferation that contributes to increased viral loads.
Previous studies have shown that depletion of CD8(+) cells during acute and chronic simian immunodeficiency virus (SIV) infection leads to increased viral replication, morbidity, and mortality, which have been attributed to loss of CD8(+) T cell-mediated control of SIV. However, these studies did not exclude that CD8(+) cell depletion increased homeostatic proliferation of CD4(+) T cells, resulting in increased viral targets and, therefore, viral rebound. Chronically SHIV89.6P-infected cynomolgus macaques were CD8(+) cell-depleted, and the frequency, cell number, and phenotype of CD4(+) T cells and viral infection were examined using flow cytometry and quantitative real-time PCR. The frequency and number of Ki-67-expressing CD4(+) T cells were increased with CD8(+) cell depletion. This proliferation of CD4(+) T cells occurred even in animals with no rebound of viral loads. Most of the proliferating cells were effector memory CD4(+) T cells. Plasma simian HIV (SHIV) RNA copies positively correlated with proliferating CD4(+) T cells and SHIV DNA copies in Ki-67(+) CD4(+) T cells. Although this study does not exclude an important role for virus-specific CD8(+) T cells in SIV and SHIV infection, our data suggest that homeostatic proliferation is an important contributor to increases in plasma viremia that follow CD8(+) cell depletion.
Department of Microbiology and Immunology, and Center for Immunology and Vaccine Sciences, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Yvonne M
YM
Mueller
Duc H
DH
Do
Jean D
JD
Boyer
Muhamuda
M
Kader
Joseph J
JJ
Mattapallil
Mark G
MG
Lewis
David B
DB
Weiner
Peter D
PD
Katsikis
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D019394:Ki-67 Antigen / Q000276:immunology; D008212:Lymphocyte Depletion; D008252:Macaca fascicularis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus; D019562:Viral Load
D019394:Ki-67 Antigen