CD8+ T-lymphocyte response to major immunodominant epitopes after vaginal exposure to simian immunodeficiency virus: too late and too little.
In the acute stage of infection following sexual transmission of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), virus-specific CD8+ T-lymphocyte responses partially control but do not eradicate infection from the lymphatic tissues (LTs) or prevent the particularly massive depletion of CD4+ T lymphocytes in gut-associated lymphatic tissue (GALT). We explored hypothetical explanations for this failure to clear infection and prevent CD4+ T-lymphocyte loss in the SIV/rhesus macaque model of intravaginal transmission. We examined the relationship between the timing and magnitude of the CD8+ T-lymphocyte response to immunodominant SIV epitopes and viral replication, and we show first that the failure to contain infection is not because the female reproductive tract is a poor inductive site. We documented robust responses in cervicovaginal tissues and uterus, but only several days after the peak of virus production. Second, while we also documented a modest response in the draining genital and peripheral lymph nodes, the response at these sites also lagged behind peak virus production in these LT compartments. Third, we found that the response in GALT was surprisingly low or undetectable, possibly contributing to the severe and sustained depletion of CD4+ T lymphocytes in the GALT. Thus, the virus-specific CD8+ T-lymphocyte response is "too late and too little" to clear infection and prevent CD4+ T-lymphocyte loss. However, the robust response in female reproductive tissues may be an encouraging sign that vaccines that rapidly induce high-frequency CD8+ T-lymphocyte responses might be able to prevent acquisition of HIV-1 infection by the most common route of transmission.
Wisconsin Primate Research Center, University of Wisconsin, Madison 53715, USA.
Matthew R
MR
Reynolds
Eva
E
Rakasz
Pamela J
PJ
Skinner
Cara
C
White
Kristina
K
Abel
Zhong-Min
ZM
Ma
Lara
L
Compton
Gnankang
G
Napoé
Nancy
N
Wilson
Christopher J
CJ
Miller
Ashley
A
Haase
David I
DI
Watkins
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D005260:Female; D016056:Immunodominant Epitopes; D007371:Interferon-gamma / Q000096:biosynthesis; D007422:Intestines / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014621:Vagina / Q000821:virology*; D014779:Virus Replication
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007371:Interferon-gamma