Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239delta3-vaccinated rhesus macaques.
Although live attenuated vaccines can provide potent protection against simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus challenges, the specific immune responses that confer this protection have not been determined. To test whether cellular immune responses mediated by CD8+ lymphocytes contribute to this vaccine-induced protection, we depleted rhesus macaques vaccinated with the live attenuated virus SIVmac239Delta3 of CD8+ lymphocytes and then challenged them with SIVmac251 by the intravenous route. While vaccination did not prevent infection with the pathogenic challenge virus, the postchallenge levels of virus in the plasmas of vaccinated control animals were significantly lower than those for unvaccinated animals. The depletion of CD8+ lymphocytes at the time of challenge resulted in virus levels in the plasma that were intermediate between those of the vaccinated and unvaccinated controls, suggesting that CD8+ cell-mediated immune responses contributed to protection. Interestingly, at the time of challenge, animals expressing the Mamu-A*01 major histocompatibility complex class I allele showed significantly higher frequencies of SIV-specific CD8+ T-cell responses and lower neutralizing antibody titers than those in Mamu-A*01- animals. Consistent with these findings, the depletion of CD8+ lymphocytes abrogated vaccine-induced protection, as judged by the peak postchallenge viremia, to a greater extent in Mamu-A*01+ than in Mamu-A*01- animals. The partial control of postchallenge viremia after CD8+ lymphocyte depletion suggests that both humoral and cellular immune responses induced by live attenuated SIV vaccines can contribute to protection against a pathogenic challenge and that the relative contribution of each of these responses to protection may be genetically determined.
Schmitz
Jörn E
JE
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, RE-113, 330 Brookline Ave., Boston, Massacusetts 02215, USA. jschmitz@bidmc.harvard.edu
Johnson
R Paul
RP
McClure
Harold M
HM
Manson
Kelledy H
KH
Wyand
Michael S
MS
Kuroda
Marcelo J
MJ
Lifton
Michelle A
MA
Khunkhun
Rajinder S
RS
McEvers
Kimberly J
KJ
Gillis
Jacqueline
J
Piatak
Michael
M
Lifson
Jeffrey D
JD
Grosschupff
Gudrun
G
Racz
Paul
P
Tenner-Racz
Klara
K
Rieber
E Peter
EP
Kuus-Reichel
Kristine
K
Gelman
Rebecca S
RS
Letvin
Norman L
NL
Montefiori
David C
DC
Ruprecht
Ruth M
RM
Desrosiers
Ronald C
RC
Reimann
Keith A
KA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015686:Gene Products, env / Q000276:immunology*; D016130:Immunophenotyping; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology*; D017384:Sequence Deletion; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity* / Q000502:physiology; D014760:Viral Fusion Proteins / Q000276:immunology*; D014765:Viral Vaccines; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015686:Gene Products, env; D015682:Retroviridae Proteins, Oncogenic; D014760:Viral Fusion Proteins; D014765:Viral Vaccines; C059580:transmembrane protein, Simian immunodeficiency virus