Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection

The rv254 cohort of hiv-infected very early acute (4thg stage 1 and 2) (stage 1/2) and late acute (4thg stage 3) (stage 3) individuals was used to study t helper- b cell responses in acute hiv infection and the impact of early antiretroviral treatment (art) on t and b cell function. to investigate this,the function of circulating t follicular helper cells (ctfh) from this cohort was examined,and ctfh and memory b cell populations were phenotyped. impaired ctfh cell function was observed in individuals treated in stage 3 when compared to stage 1/2. the ctfh/b cell cocultures showed lower b cell survival and igg secretion at stage 3 compared to stage 1/2. this coincided with lower il-10 and increased rantes and tnf-α suggesting a role for inflammation in altering ctfh and b cell responses. elevated plasma viral load in stage 3 was found to correlate with decreased ctfh-mediated b cell igg production indicating a role for increased viremia in ctfh impairment and dysfunctional humoral response. phenotypic perturbations were also evident in the mature b cell compartment,most notably a decrease in resting memory b cells in stage 3 compared to stage 1/2,coinciding with higher viremia. our coculture assay also suggested that intrinsic memory b cell defects could contribute to the impaired response despite at a lower level. overall,ctfh-mediated b cell responses are significantly altered in stage 3 compared to stage 1/2,coinciding with increased inflammation and a reduction in memory b cells. these data suggest that early art for acutely hiv infected individuals could prevent immune dysregulation while preserving ctfh function and b cell memory. © 2016 muir et al.