Abstract
CD8+ T cells play an important role in controlling of HIV and SIV infections. However, these cells are largely excluded from B cell follicles where HIV and SIV producing cells concentrate during chronic infection. It is not known, however, if antigen-specific CD8+ T cells are excluded gradually as pathogenesis progresses from early to chronic phase, or this phenomenon occurs from the beginning infection. In this study we determined that SIV-specific CD8+ T cells were largely excluded from follicles during early infection, we also found that within follicles, they were entirely absent in 60% of the germinal centers (GCs) examined. Furthermore, levels of SIV-specific CD8+ T cells in follicular but not extrafollicular areas significantly correlated inversely with levels of viral RNA+ cells. In addition, subsets of follicular SIV-specific CD8+ T cells were activated and proliferating and expressed the cytolytic protein perforin. These studies suggest that a paucity of SIV-specific CD8+ T cells in follicles and complete absence within GCs during early infection may set the stage for the establishment of persistent chronic infection.
Highlights
Most human immunodeficiency virus (HIV)-infected individuals fail to adequately control persistent high-level viral replication that results in gradual loss of CD4 T cells and AIDS in the absence of antiretroviral therapy (ART)
A paucity of simian immunodeficiency virus (SIV)-specific CD8+ T cells in lymphoid follicles and complete absence within most follicular germinal centers during early infection may set the stage for the establishment of persistent chronic infection
SIV-specific CD8+ T cells are largely excluded from germinal centers (GCs) during early infection
Summary
Most human immunodeficiency virus (HIV)-infected individuals fail to adequately control persistent high-level viral replication that results in gradual loss of CD4 T cells and AIDS in the absence of antiretroviral therapy (ART). The paucity of virus-specific CD8+ T cells inside B cell follicles, where HIV- and SIV-producing cells are highly concentrated, creates an immune privileged site and an important mechanism of immune evasion by HIV and SIV This mechanism may, at least partially, account for the failure of CD8+ T cells to fully eradicate HIV and SIV infections. Studies indicate that there are populations of functional CD8+ T cells expressing CXCR5 in B cell follicles in chronic LCMV, HIV and SIV infections [20,22,23], and levels of follicular virus-specific CD8+ T cells correlate with reductions of plasma viral loads and tissue viral replication [3,20,24,25]. In this study, we determined the abundance, distribution and phenotype of SIV-specific T cells in lymph nodes from a cohort of SIV infected rhesus macaques during the early stages of infection
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