CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells.
While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.
Klatt
Nichole R
NR
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Shudo
Emi
E
Ortiz
Alex M
AM
Engram
Jessica C
JC
Paiardini
Mirko
M
Lawson
Benton
B
Miller
Michael D
MD
Else
James
J
Pandrea
Ivona
I
Estes
Jacob D
JD
Apetrei
Cristian
C
Schmitz
Joern E
JE
Ribeiro
Ruy M
RM
Perelson
Alan S
AS
Silvestri
Guido
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018925:Chemokines / Q000097:blood; D003602:Cytotoxicity, Immunologic; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D008962:Models, Theoretical; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication / Q000276:immunology*
D018925:Chemokines