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

PLoS Pathog. 2016 Jul 27;12(7):e1005777. doi: 10.1371/journal.ppat.1005777. eCollection 2016 Jul.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • B-Lymphocytes / immunology*
  • Coculture Techniques
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • HIV Infections / immunology*
  • HIV-1 / immunology
  • Humans
  • Immunologic Memory / immunology*
  • Lymphocyte Activation / immunology
  • Male
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Viral Load

Substances

  • Anti-HIV Agents