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
Department of Pediatrics, Section of Pediatric Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Department of Medicine, Section of Pediatric Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Front Immunol. 2018 Jan 19;8:2002. doi: 10.3389/fimmu.2017.02002. eCollection 2017.
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.
我们在接受抗逆转录病毒治疗的围产期感染艾滋病毒（PHIV）婴儿以及参与国际母婴儿科青少年艾滋病临床试验P1072研究（NCT00880698）的未感染艾滋病毒但暴露于艾滋病毒的婴儿（PHEU）中，研究了B细胞和T细胞表型特征与五价轮状病毒疫苗（RV5）抗体反应之间的关联。在分析的17个B细胞和T细胞亚群中，PHIV组和PHEU组仅在CD4 + T细胞数量和幼稚B细胞频率上存在差异，PHEU组高于PHIV组。相比之下，PHIV组和PHEU组的B细胞和T细胞表型特征与地理匹配的当代未暴露于艾滋病毒的婴儿明显不同。PHIV组和PHEU组调节性T细胞和B细胞（Treg、Breg）的频率呈现出两种关联模式：FOXP3 + CD25 + Treg与CD4 + T细胞数量呈正相关；而TGFβ + Treg、IL10 + Treg和Breg与炎症性和活化T细胞的频率呈正相关。此外，PHIV组和PHEU组活化和炎症性T细胞的频率与未成熟B细胞的频率呈正相关。这些相关性不受艾滋病毒感染状态的影响，且随时间持续存在。与慢性艾滋病毒感染中先前描述的情况类似，PHIV组和PHEU组对RV5的抗体反应与CD4 + T细胞计数呈正相关，与未成熟B细胞的比例呈负相关。PHIV组和PHEU组特有的情况是，抗RV5抗体与CD4 + /CD8 + FOXP3 + CD25 + %呈正相关，与CD4 + IL10 + % Tregs呈负相关。总之，PHEU组与PHIV组具有异常的B细胞和T细胞表型特征。除了CD4 + /CD8 + FOXP3 + CD25 + Treg与抗体产生增加之间的关联外，PHIV组和PHEU组对RV5的抗体反应受到典型的艾滋病毒相关免疫反应调节因子的调节。
