Proportions of circulating follicular helper T cells are reduced and correlate with memory B cells in HIV-infected children

Abstract

IntroductionHIV causes defects in memory B cells in children, but the mechanisms of those defects have not been fully elucidated. One possible mechanism is the lack of T-cell help to B cells during immune reactions. However, few studies have assessed the effect of HIV on follicular helper T cells (TFH cells) in children.MethodsIn this study, follicular-homing CD4 T cells and memory B cells were assessed in HIV-infected children and compared with children from the community. CXCR5 and CD45RO were used as markers of follicular-homing T cells and memory T cells, respectively. Memory TFH cells were identified as CD3+CD8-CD4+CXCR5+CD45RO+PD1+. Central memory T cells were identified based on CCR7 expression. Relationship between the proportions of follicular-homing CD4 T cells and memory B cells were determined in multivariable regression models.ResultsHighly viremic HIV-infected children had lower proportions of memory TFH cells when compared with community control children. In multivariable analyses, high proportions of memory TFH cells were associated with increased percentages of resting memory B cells after adjusting for other covariates.ConclusionThe impact of HIV on follicular helper T cells could influence the accumulation of memory B cells in HIV-infected children.

Early HIV infection is associated with reduced proportions of gamma delta T subsets as well as high creatinine and urea levels

“…Also, as observed in our study, treated LVL groups had higher proportions of naïve and memory B cells compared with HVL. This supports previous studies which suggest that high viremia impacts B cell reconstitution after ART exposure . We also observed that memory B cells defined by (CD19 + CD27) were increased during early HIV compared with the chronic stage before commencement of ART.…”

“…γδ T cells have been shown to regulate humoral responses including autoantibodies, modulate size and production of preimmune peripheral B cells as well as control levels of circulating immunoglobulins . It has been previously shown that memory B cells defects during HIV infection may be due to the impact of the virus on T cells that provide B cells help in germinal centers . As observed in previous studies, treated HVL and LVL groups had significantly higher proportions of the naïve and memory B cells compared with other groups .…”

“…Chronic immune activation, which is a hallmark of HIV infection, has been shown recently to be significantly overexpressed at the first month of infection after which it undergoes a prompt decrease before another rapid increase towards seroconversion . The initial overexpression may coincide with the period of high viral replication and seeding into various cellular reservoirs .…”

HIV Replication in Humanized IL-3/GM-CSF-Transgenic NOG Mice

“…Indeed, B-cells depletion in HIV is associated with increased susceptibility to CD95 ligand-mediated cell death [47], as well as intrinsic apoptosis [48]. CXCR5 + CD4 + T-cells, both circulating and follicle-confined, are relevant in HIV infection as they are a major target of this virus, constitute the main viral reservoir [49,50], and they have been found decreased in blood [51,52] but expanded in lymph nodes from HIV-infected patients [53]. However, there were no differences in the frequencies of CXCR5 + CD4 + T-cells between HIV-infected and uninfected huNOG-EXL mice, both in blood and SLO (Figure 6C).…”

Global Assessment of Dengue Virus-Specific CD4+ T Cell Responses in Dengue-Endemic Areas

“…This suggests that, in parallel with antibody response, T cell responses should be measured and analyzed to achieve a complete assessment of DENV-specific adaptive immunity. In addition, peripheral CD4 + T cells probably contain a fraction of circulating memory follicular T helper cells that are relevant for B cell differentiation and the production of neutralizing antibodies ( 38 , 39 ). Since DENV infection and disease is a worldwide and ever-increasing problem, a global approach to assess T cell responses in different human populations is required.…”