*These authors equally contributed to the manuscript Corresponding author:

Generation of antibody-secreting plasma cells critically depends upon CD4 T follicular helper (TFH) cells during the germinal center (GC) reaction. GC TFH cells share functional properties with circulating CXCR5+ CD4 T cells, referred to as peripheral TFH (pTFH). Since deficient antibody production and CD4 T cell loss are recognized features of HIV infection, we investigated pTFH cells in 25 HIV-infected patients on antiretroviral therapy. pTFH frequency was equivalent in patients and healthy controls (HC), and these cells displayed a central memory phenotype. Sixteen patients and 8 HC in this group were given a single dose of H1N1/09 influenza vaccine during the 2009 H1N1 influenza outbreak. In the vaccine responder patients (n=8) and HC, 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 non responder patients (n=8). In co-culture experiments, sorted pTFH cells supported HIN1-stimulated IgG production by autologous B cells only in vaccine responders. At T2, frequencies of pTFH correlated with memory B cells, serum H1N1 antibody titers and antigen-induced IL-21 secretion. Characterization of pTFH cells may provide additional insight int