(111)]

(111)]. infected people experience increased risk of age-associated pathologies. This review will discuss Tfh and B cell dysfunction in HIV contamination and spotlight the impact of chronic HIV contamination and aging on TfhCB cell interactions. Phentolamine HCl stimulation with H1N1 resulting in induction of CXCR5 mRNA and protein in CD4 T cells and (ii) induction of gene in pTfh cells. These antigen-specific prevaccination steps strongly associated with H1N1-specific B cell responses by ELISPOT at postvaccination (91). Interestingly, CD4 T cells from VNR exhibit increased expression of and genes, which are known to antagonize pTfh function (92). Our main findings of pTfh and B cells in relation to vaccine responses are summarized in Table ?Table1.1. Other vaccine studies have shown associations between pTfh growth and phenotype with vaccine response. Growth of HIV-specific PD-1?+?ICOS?+?pTfh correlated with vaccine-specific serum IgG after booster immunization in three different human HIV vaccine trials (93). Expression of ICOS, PD-1, CD38, and IL-21 in pTfh subsets have been useful for evaluating the influenza vaccine response in HIV-infected and -uninfected adults in other studies as well (50, 87, 93C95). Studies with Ebola vaccine (rVSV-ZEB OV) exhibited that CXCR5?+?PD-1?+?pTfh correlated with expansion of plasmablasts (96). Taken together, these studies support the concept that both quality and quantity of pTfh cells are important determinants for the outcome of vaccine response in HIV contamination. Table 1 Signature immunological changes in pTfh and B cells in vaccine responders (VRs) following influenza vaccine at TO (baseline), T1 (7?days), and T2 (4?weeks). Changes in pTfh cell compartment in vaccine respondersAntigen induced IL-21 gene expression at TO Growth of pTfh at T1, T2 Ag-stimulated intracellular IL-21 production in pTfh at T2 Help to autologous B cells for H1N1-specific IgG production and B cell differentiation in pTfh plus B cell cocultures at T2 B cell changes in vaccine respondersIncrease in frequencies of plasmablasts at T1 Increase in spontaneous H1N1-specific ASC at T1 Increase in memory B cells and switch memory at T2 Upregulation of IL-21R on total B and memory B cells at T2 Increase in TACI expression on total B and memory B cells at T2 Downregulation of BAFT-R expression on total B and memory B cells at T2 PBMC culture sups/plasma findings in vaccine respondersProduction of IL-21 and CXCL13 in H1N1-stimulated culture sups with increases in plasma IL-21 Increase in plasma BAFF and APRIL levels Open in a separate windows em pTfh, peripheral T follicular helper; PBMCs, peripheral blood mononuclear cells; Ab, antibody; BAPF-R, B cell activating factor receptor; APRIL, a proliferation inducing Phentolamine HCl ligand; CXCL13, C-X-C Rabbit Polyclonal to PAK5/6 motif chemokine ligand 13; ASCs, antibody secreting cells /em . Tfh Cells and B Cells in HIV and Aging Our group has been interested in the question of immune function of aging HIV+ individuals who are well controlled on ART, the extent to which it resembles biologic aging of HIV? individuals, and implications of aging with HIV contamination. Earlier pilot studies in virologically suppressed postmenopausal women as representative of an aging population established the persistence of inflammation and gut microbial translocation and detrimental role of underlying immune activation on influenza vaccine responses that were associated with quantitative and qualitative deficiencies of pTfh cells (45, 97, 98). Our studies showed lower H1N1 influenza antibody titers in HIV-infected women compared to HIV-uninfected women at prevaccination. Following vaccination, magnitude of antibody responses and frequency of study participants achieving seroprotective titers were lower in HIV+ than in HIV? women. Frequencies of pTfh cells at postvaccination correlated with memory B cell function and H1N1 antibody titers. Antibody responses postvaccination were inversely correlated with inflammatory cytokine TNF in plasma and with markers of cellular immune activation (CD38 and HLA-DR) on CD4 T cells, including pTfh subset, indicating an adverse influence of baseline immune activation and inflammation on vaccine induced antibody response in older age. To examine the role of age and HIV contamination further, we are engaged in a large ongoing study (99, 100) in virologically suppressed HIV+ and HIV? adults grouped by age as young ( 40?years), middle aged (40C59?years), and old (60?years). Following seasonal trivalent influenza vaccine (TIV), magnitude of Ab titers against each vaccine strain were found to be lower in old age compared to others, regardless of HIV status. Baseline titers Phentolamine HCl in seroprotective range were higher.