Chronic HIV-1 Infection Impairs Superantigen-Induced Activation of Peripheral CD4+CXCR5+PD-1+ Cells, With Relative Preservation of Recall Antigen-Specific Responses.

Peripheral CD4+ CXCR5+ PD-1+T cells are a putative circulating counterpart to germinal center T follicular helper (T-FH) cells. They show both phenotypic and functional similarities to T-FH cells, which provide necessary help for the differentiation of B cells to antibody-secreting plasmablasts. In this study, we evaluated the frequency, phenotypes, and responses of peripheral T-FH-like (pT(FH)) cells to superantigen and recall antigen stimulation in 10 healthy and 34 chronically infected treatment-naive HIV-1+ individuals. There was no difference in the frequency of pTFH cells between HIV+ and HIV- individuals. Surface expression of ICOS, but not CD40L, was higher on pTFH cells at baseline in HIV+ individuals. Compared with HIV- individuals, pT(FH) cells from HIV+ individuals had decreased maximal expression of ICOS and CD40L in response to in vitro superantigen stimulation. This decreased response did not correlate with viral control, CD4(+) T-cell count, duration of infection, or the degree of neutralizing antibody breadth. Despite a decreased maximal response, pT(FH) responses to HIV Gag and tetanus toxoid recall antigens were preserved.