title: Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection.
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.
authors.affiliation: Drexel University, Department of Medicine, Division of Infectious Diseases & HIV Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Roshell
authors.initials: R
authors.lastname: Muir
authors.affiliation: Drexel University, Department of Medicine, Division of Infectious Diseases & HIV Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Talibah
authors.initials: T
authors.lastname: Metcalf
authors.affiliation: Drexel University, Department of Medicine, Division of Infectious Diseases & HIV Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Virginie
authors.initials: V
authors.lastname: Tardif
authors.affiliation: 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.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takata
authors.affiliation: SEARCH, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
authors.affiliation: SEARCH, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Eugene
authors.initials: E
authors.lastname: Kroon
authors.affiliation: SEARCH, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Donn J
authors.initials: DJ
authors.lastname: Colby
authors.affiliation: Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, United States Component, Bangkok, Thailand.
authors.forename: Rapee
authors.initials: R
authors.lastname: Trichavaroj
authors.affiliation: Memory and Aging Center, University of California, San Francisco, United States of America.
authors.forename: Victor
authors.initials: V
authors.lastname: Valcour
authors.affiliation: 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.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: United States Military HIV Research Program, Bethesda, Maryland, United States of America.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: 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.|SEARCH, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.affiliation: 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.
authors.forename: Lydie
authors.initials: L
authors.lastname: Trautmann
authors.affiliation: Drexel University, Department of Medicine, Division of Infectious Diseases & HIV Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Elias K
authors.initials: EK
authors.lastname: Haddad
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology*; D018920:Coculture Techniques; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents