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

PLoS Pathogens

Victor Valcour¹  Roshell Muir²  Talibah Metcalf²  Virginie Tardif²  Merlin L. Robb³  Rapee Trichavaroj⁴  Eugene Kroon⁴  Donn J. Colby⁴  Nelson L. Michael⁵  Hiroshi Takata⁵  Elias K. Haddad⁵  Nittaya Phanuphak⁶  RV254/SEARCH010 RV304/SEARCH 013 Study Groups⁶  Lydie Trautmann⁶  Jintanat Ananworanich⁶ 

[1] Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, United States Component, Bangkok, Thailand;Drexel University, Department of Medicine, Division of Infectious Diseases & HIV Medicine, Philadelphia, Pennsylvania, United States of America;Memory and Aging Center, University of California, San Francisco, United States of America;SEARCH, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand;The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America;United States Military HIV Research Program, Bethesda, Maryland, United States of America

关键词: B cells;    Memory B cells;    HIV infections;    Viral load;    HIV;    Cytokines;    T cells;    Graphs;   

DOI  :  10.1371/journal.ppat.1005777

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY