SIV-specific CD8 T cells are largely excluded from B cell follicles during early SIV infection

Abstract

Abstract While HIV− and SIV-specific CD8 T cell responses are critical for suppression of virus producing cells, these cells fail to fully suppress viral replication. During chronic infection, one potential mechanism for this failure is relatively low levels of virus-specific CD8 T cells in B cell follicles, where virus is most concentrated, permitting ongoing virus replication. It is not known whether this phenomenon also occurs during early infection. Here, we determined the location, abundance, and phenotype of SIV-specific CD8 T cells in lymph nodes from SIV-infected rhesus macaques at 21 days post-infection. We found that levels of SIV-specific CD8 T cells in B cell follicles were significantly lower than in extrafollicular regions. Within follicles, SIV-specific CD8 T cells were largely excluded from germinal centers. A median of 62% of follicular SIV-specific CD8 T cells expressed PD-1. In addition, a median of 12% of follicular SIV-specific CD8 T cells were in direct contact with Foxp3+ cells, and 4% were themselves Foxp3+. Ki67 was expressed by a median of 41% of follicular SIV-specific CD8 T cells and 25% expressed high levels of perforin. These data suggest that during early stages of infection, low levels of follicular SIV-specific CD8 T cells may permit ongoing viral replication, similar to what we previously reported in chronic disease. Furthermore, these data suggest that follicular SIV-specific CD8 T cells are possibly exhausted, that subsets may be inhibited by Foxp3+ Tregs, that subsets are activated and dividing, and subsets express the effector molecule perforin suggesting cytolytic potential. These findings provide important insights into SIV immunopathogenesis and may help inform future cure strategies.