Increased loss of CCR5+ CD45RA- CD4+ T cells in CD8+ lymphocyte-depleted Simian immunodeficiency virus-infected rhesus monkeys.
Previously we have shown that CD8(+) T cells are critical for containment of simian immunodeficiency virus (SIV) viremia and that rapid and profound depletion of CD4(+) T cells occurs in the intestinal tract of acutely infected macaques. To determine the impact of SIV-specific CD8(+) T-cell responses on the magnitude of the CD4(+) T-cell depletion, we investigated the effect of CD8(+) lymphocyte depletion during primary SIV infection on CD4(+) T-cell subsets and function in peripheral blood, lymph nodes, and intestinal tissues. In peripheral blood, CD8(+) lymphocyte-depletion changed the dynamics of CD4(+) T-cell loss, resulting in a more pronounced loss 2 weeks after infection, followed by a temporal rebound approximately 2 months after infection, when absolute numbers of CD4(+) T cells were restored to baseline levels. These CD4(+) T cells showed a markedly skewed phenotype, however, as there were decreased levels of memory cells in CD8(+) lymphocyte-depleted macaques compared to controls. In intestinal tissues and lymph nodes, we observed a significantly higher loss of CCR5(+) CD45RA(-) CD4(+) T cells in CD8(+) lymphocyte-depleted macaques than in controls, suggesting that these SIV-targeted CD4(+) T cells were eliminated more efficiently in CD8(+) lymphocyte-depleted animals. Also, CD8(+) lymphocyte depletion significantly affected the ability to generate SIV Gag-specific CD4(+) T-cell responses and neutralizing antibodies. These results reemphasize that SIV-specific CD8(+) T-cell responses are absolutely critical to initiate at least partial control of SIV infection.
Veazey
Ronald S
RS
Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana 70433, USA.
Acierno
Paula M
PM
McEvers
Kimberly J
KJ
Baumeister
Susanne H C
SH
Foster
Gabriel J
GJ
Rett
Melisa D
MD
Newberg
Michael H
MH
Kuroda
Marcelo J
MJ
Williams
Kenneth
K
Kim
Eun-Young
EY
Wolinsky
Steven M
SM
Rieber
E Peter
EP
Piatak
Michael
M
Lifson
Jeffrey D
JD
Montefiori
David C
DC
Brown
Charles R
CR
Hirsch
Vanessa M
VM
Schmitz
Jörn E
JE
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D018450:Disease Progression; D015683:Gene Products, gag / Q000276:immunology; D007422:Intestines / Q000166:cytology / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008297:Male; D019713:Receptors, CCR5 / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015996:Survival Rate; D014779:Virus Replication
D000914:Antibodies, Viral; D015683:Gene Products, gag; D019713:Receptors, CCR5; D017493:Leukocyte Common Antigens