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Journal article
Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection
PLoS pathogens, v 12(7), pp e1005777-e1005777
Jul 2016
PMID: 27463374
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection
- Creators
- Roshell Muir - Drexel UniversityTalibah Metcalf - Drexel UniversityVirginie Tardif - Drexel UniversityHiroshi Takata - Henry M. Jackson FoundationNittaya Phanuphak - SEARCH, the Thai Red Cross AIDS Research Centre, Bangkok, ThailandEugene Kroon - Thai Red Cross SocietyDonn J Colby - Thai Red Cross SocietyRapee Trichavaroj - Armed Forces Research Institute of Medical ScienceVictor Valcour - University Memory and Aging CenterMerlin L Robb - Henry M. Jackson FoundationNelson L Michael - United States Military HIV Research ProgramJintanat Ananworanich - Henry M. Jackson FoundationLydie Trautmann - Henry M. Jackson FoundationElias K Haddad - Drexel UniversityRV254/SEARCH010 RV304/SEARCH 013 Study Groups
- Publication Details
- PLoS pathogens, v 12(7), pp e1005777-e1005777
- Publisher
- Public LIbrary of Science (PLOS)
- Grant note
- R01 AI108433 / NIAID NIH HHS R01 AI106482 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000383366400049
- Scopus ID
- 2-s2.0-84982994525
- Other Identifier
- 991019167987404721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Microbiology
- Parasitology
- Virology