CD4 T cell subsets in the mucosa are CD28⁺Ki-67^-HLA-DR^-CD69⁺ but show differential infection based on α4β7 receptor expression during acute SIV infection

Background: CD4 T cell depletion in the mucosa has been well documented during acute HIV and SIV infections. The demonstration the HIV/SIVcan use the α4β7 receptor for viral entry suggests that these viruses selectively target CD4 T cells in the mucosa that express high levels of α4β7 receptor. Methods: Mucosal samples obtained from SIV infected rhesus macaques during the early phase of infection were used for immunophenotypic analysis. CD4 T cell subsets were sorted based on the expression of β7 and CD95 to quantify the level of SIV infection in different subsets of CD4 T cells. Changes in IL-17, IL-21, IL-23 and TGFβ mRNA expression was determined using Taqman PCR. Results: CD4 T cells in the mucosa were found to harbor two major population of cells; -25% of CD4 T cells expressed the α4⁺β7^hi phenotype, whereas the rest of the 75% expressed an α4⁺β7^int phenotype. Both the subsets were predominantly CD28⁺Ki-67^-HLA-DR^- but CD69⁺, and expressed detectable levels of CCR5 on their surface. Interestingly, however, α4⁺β7^hiCD4 T cells were found to harbor more SIV than the α4⁺β7^int subsets at day 10 pi. Early infection was associated with a dramatic increase in the expression of IL-17, and IL-17 promoting cytokines IL-21, IL-23, and TGFβ that stayed high even after the loss of mucosal CD4 T cells. Conclusions: Our results suggest that the differential expression of the α4β7 receptor contributes to the differences in the extent of infection in CD4 T cell subsets in the mucosa. Early infection is associated dysregulation of the IL-17 network in mucosal tissues involves other non-Th-17 cells that likely contributes to the pro-inflammatory environment in the mucosa during acute stages of SIV infection.