Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine

Abstract

The generation of Ab-secreting plasma cells depends critically on CD4 T-follicular helper (TFH) cells during the germinal center reaction. Germinal center TFH cells share functional properties with circulating CXCR5 CD4 T cells, referred to herein as peripheral TFH (pTFH) cells. Because deficient Ab production and CD4 T-cell loss are recognized features of HIV infection , in the present study, we investigated pTFH cells in 25 HIV-infected patients on antiretroviral therapy. pTFH frequency was equivalent in patients and healthy controls (HCs), and these cells displayed a central memory phenotype. Sixteen patients and 8 HCs in this group were given a single dose of H1N1/09 influenza vaccine during the 2009 H1N1 influenza outbreak. In the vaccine responders (n 8) and HCs, pTFH cells underwent expansion with increased IL-21 and CXCL13 secretion in H1N1-stimulated PBMC culture supernatants at week 4 (T2). These changes were not seen in vaccine nonre-sponders (n 8). In coculture experiments , sorted pTFH cells supported HIN1-stimulated IgG production by autologous B cells only in vaccine responders. At T2, frequencies of pTFH were correlated with memory B cells, serum H1N1 Ab titers, and Ag-induced IL-21 secretion. Characterization of pTFH cells may provide additional insight into cellular determinants of vaccine-induced Ab response, which may have relevance for vaccine design. (Blood. 2012;120(5):985-993)

Human circulating influenza-CD4 + ICOS1 + IL-21 + T cells expand after vaccination, exert helper function, and predict antibody responses

“…We show that the expansion of avian or seasonal influenza CXCR5 − ICOS1 + IL-21 + CD4 + T cells, 3 wk after vaccination, is associated with the increase in neutralizing antibodies. Our identification of CXCR5 − T cells as responsible for this function is in disagreement with previous results in mice and humans (3,5,9,12,17,25). We believe the analysis of lymphoid tissue vs. blood, as well as differences in the experimental procedure, can explain such discrepancies.…”

Reevaluation of immune activation in the era of cART and an aging HIV-infected population

“…The relevance of these data are unclear and may point to aberrant IL-21 signaling in HIV + individuals that may be inhibitory for immune function and especially Tfh-mediated B cell responses to vaccination. Induction of IL-21 following vaccination may be a more relevant biomarker, as IL-21-producing CD4 + T cells in the circulation, recognized as pTfh, have been shown to correlate with Ab responses to vaccination (22,48,49). We found an association of pTfh frequency with vaccine response in HC, while in HIV + , specific IA marker expression on pTfh was predictive and cell frequency was not associated.…”

Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

“…At baseline, HIV infection was associated with reduced Fc-mediated Ab functionality, despite similar serological HI activity to HIV-negative subjects. Although the reason for more-severe influenza infections in HIVpositive subjects is almost certainly multifactorial (20,(33)(34)(35), our results suggest that a reduction in Abs able to effectively interact with FcR may contribute to this increased risk. We detected NK cell-activating Abs to HA from the novel circulating influenza virus strain A/Switzerland/9715293/2013 in the majority (93%) of both HIV-negative and HIV-positive subjects in the absence of HI responses to this strain.…”