Production of IgG2 Antibodies to Pneumococcal Polysaccharides After Vaccination of Treated HIV Patients May Be Augmented by IL-7Rα Signaling in ICOS + Circulating T Follicular-Helper Cells.

Greater understanding of factors influencing the maturation of antibody responses against pneumococcal polysaccharides (PcPs) may improve pneumococcal vaccination strategies. Although PcPs are type 2 T cell-independent antigens thought not to induce follicular immune responses, we have previously shown that IgG2 antibody responses against antigens in the 23-valent unconjugated PcP vaccine (PPV23) are associated with expansion of ICOS+ circulating T follicular helper (cT(FH)) cells in HIV seronegative subjects but not HIV patients. As IL-7R alpha signaling in CD4(+) T cells may affect T-FH cell function and is adversely affected by HIV-1 infection, we have examined the relationship of IL-7R alpha expression on ICOS+ cT(FH) cells with PcP-specific IgG2 antibody responses. PPV23 vaccination was undertaken in HIV patients receiving antiretroviral therapy (n = 25) and HIV seronegative subjects (n = 20). IL-7R alpha expression on ICOS+ and ICOS- cT(FH) cells was assessed at day(D) 0, 7, and 28. Fold increase between D0 and D28 in serum IgG1 and IgG2 antibodies to PcP serotypes 4, 6B, 9V, and 14 and the frequency of IgG1(+) and IgG2(+) antibody secreting cells (ASCs) at D7 were also assessed. Decline in IL-7R alpha expression on ICOS+ cT(FH) cells between D0 and D7 occurred in 75% of HIV seronegative subjects and 60% of HIV patients (Group A), with changes in IL-7R alpha expression being more pronounced in HIV patients. Group A patients exhibited abnormally high IL-7R alpha expression pre-vaccination, an association of serum IgG2, but not IgG1, antibody responses with a decline of IL-7R alpha expression on ICOS+ cT(FH) cells between D0 and D7, and an association of higher IgG2(+) ASCs with lower IL-7R alpha expression on ICOS+ cT(FH) cells at D7. As decline of IL-7R alpha expression on CD4(+) T cells is an indicator of IL-7R alpha signaling, our findings suggest that utilization of IL-7 by cT(FH) cells affects production of IgG2 antibodies to PPV23 antigens in some HIV patients.