期刊
AIDS
卷 28, 期 10, 页码 1421-1430出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000000292
关键词
cytokines; infants; maternal HIV; proliferation; T-cell immunity; vaccination
资金
- Elizabeth Glaser Pediatric AIDS Foundation [MV-00-9-900-01871-0-00]
- Thrasher Foundation [NR-0095]
- University of Washington Center for AIDS Research Developmental award [P30AI027757]
Objective: In sub-Saharan Africa, HIV-exposed uninfected (HEU) infants have higher morbidity and mortality than HIV-unexposed infants. To evaluate whether immune dysfunction contributes to this vulnerability of HEU infants, we conducted a longitudinal, observational cohort study to assess T-cell immune responses to infant vaccines (Mycobacterium bovis BCG and acellular pertussis) and staphylococcal enterotoxin B (SEB). In total, 46 HEU and 46 HIV-unexposed infants were recruited from Khayelitsha, Cape Town. Methods: Vaccine-specific T-cell proliferation (Ki67 expression) and intracellular expression of four cytokines [interferon-g, interleukin (IL)-2, IL-13 and IL-17] were measured after whole blood stimulation with antigens at 6 and 14 weeks of age. Results: HEU infants demonstrated elevated BCG-specific CD4(+) and CD8(+) T-cell proliferative responses at 14 weeks (P = 0.041 and 0.002, respectively). These responses were significantly increased even after adjusting for birth weight, feeding mode and gestational age. Similar to BCG, increased CD4(+) and CD8(+) T-cell proliferation was evident in response to SEB stimulation (P = 0.004 and 0.002, respectively), although pertussis-specific T cells proliferated comparably between the two groups. Within HEU infants, maternal CD4(+) cell count and length of antenatal antiretroviral exposure had no effect on T-cell proliferation to BCG or SEB. HIV exposure significantly diminished measurable cytokine polyfunctionality in response to BCG, Bordetella pertussis and SEB stimulation. Conclusion: These data show for the first time, when adjusting for confounders, that exposure to HIV in utero is associated with significant alterations to CD4(+) and CD8(+) T-cell immune responses in infants to vaccines and nonspecific antigens. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
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