AUTHOR=Weinberg Adriana , Lindsey Jane , Bosch Ronald , Persaud Deborah , Sato Paul , Ogwu Anthony , Asmelash Aida , Bwakura-Dangarambezi Mutsa , Chi Benjamin H. , Canniff Jennifer , Lockman Shahin , Gaseitsiwe Simani , Moyo Sikhulile , Smith Christiana Elizabeth , Moraka Natasha O. , Levin Myron J. , for the P1072 and Tshipidi Study Teams , Fane Charles , Kooreng Dudu , Kakhu Tebogo J. , Mazhani Loeto , Sekoto Tumalano , Tirelo Lesedi , Frank Tshepo T. , Raesi Mpho , Kinabo Grace , Njau Boniface , Buchanan Anne , Kimaro Janeth , Mbewe Felistus , Shingalili Ellen , Chirwa Fyatilani , Mulenga Helen Bwalya , Mbengeranwa Tapiwa , Beta Taurai , Dauya Ethel , Mujuru Hilda TITLE=B and T Cell Phenotypic Profiles of African HIV-Infected and HIV-Exposed Uninfected Infants: Associations with Antibody Responses to the Pentavalent Rotavirus Vaccine JOURNAL=Frontiers in Immunology VOLUME=8 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.02002 DOI=10.3389/fimmu.2017.02002 ISSN=1664-3224 ABSTRACT=

We examined associations between B and T cell phenotypic profiles and antibody responses to the pentavalent rotavirus vaccine (RV5) in perinatally HIV-infected (PHIV) infants on antiretroviral therapy and in HIV-exposed uninfected (PHEU) infants enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials P1072 study (NCT00880698). Of 17 B and T cell subsets analyzed, PHIV and PHEU differed only in the number of CD4+ T cells and frequency of naive B cells, which were higher in PHEU than in PHIV. In contrast, the B and T cell phenotypic profiles of PHIV and PHEU markedly differed from those of geographically matched contemporary HIV-unexposed infants. The frequency of regulatory T and B cells (Treg, Breg) of PHIV and PHEU displayed two patterns of associations: FOXP3+ CD25+ Treg positively correlated with CD4+ T cell numbers; while TGFβ+ Treg and IL10+ Treg and Breg positively correlated with the frequencies of inflammatory and activated T cells. Moreover, the frequencies of activated and inflammatory T cells of PHIV and PHEU positively correlated with the frequency of immature B cells. Correlations were not affected by HIV status and persisted over time. PHIV and PHEU antibody responses to RV5 positively correlated with CD4+ T cell counts and negatively with the proportion of immature B cells, similarly to what has been previously described in chronic HIV infection. Unique to PHIV and PHEU, anti-RV5 antibodies positively correlated with CD4+/CD8+FOXP3+CD25+% and negatively with CD4+IL10+% Tregs. In conclusion, PHEU shared with PHIV abnormal B and T cell phenotypic profiles. PHIV and PHEU antibody responses to RV5 were modulated by typical HIV-associated immune response modifiers except for the association between CD4+/CD8+FOXP3+CD25+Treg and increased antibody production.