Weinberg Adriana, Muresan Petronella, Richardson Kelly, Fenton Terence, Dominguez Teresa, Bloom Anthony, Watts D Heather, Abzug Mark J, Nachman Sharon A, Levin Myron J
1 University of Colorado Anschutz Medical Campus , Aurora, Colorado.
2 Statistical and Data Analysis Center, Center for Biostatistics in AIDS Research , Harvard School of Public Health, Boston, Massachusetts.
AIDS Res Hum Retroviruses. 2015 Nov;31(11):1170-7. doi: 10.1089/aid.2015.0151. Epub 2015 Aug 31.
We investigated the Th1 protective and regulatory T and B cell (Treg and Breg) responses to pH1N1 monovalent influenza vaccine (IIV1) in HIV-infected pregnant women on combination antiretroviral therapy (cART). Peripheral blood mononuclear cells (PBMCs) from 52 study participants were cryopreserved before and after vaccination and analyzed by flow cytometry. pH1N1-specific Th1, Treg, and Breg responses were measured in PBMCs after in vitro stimulation with pH1N1 and control antigen. The cohort analysis did not detect changes in pH1N1-Th1, Treg, or Breg subsets postvaccination. However, individual analyses distinguished subjects who mounted vigorous Th1 responses postvaccination from others who did not. Postvaccination, high pH1N1-Th1 correlated with high pH1N1-Treg and Breg responses, suggesting that low influenza effector responses did not result from excessive vaccine-induced immune regulation. High postvaccination pH1N1-Th1 responses correlated with baseline high PHA- and pH1N1-IFN-γ ELISpot and circulating CD4(+)CD39(+)% and CD8(+)CD39(+)% Treg, with low CD8(+) cell numbers and CD19(+)FOXP3(+)% Breg, but not with CD4(+) cell numbers or HIV viral load. These data highlight the heterogeneity of T cell responses to vaccines in HIV-infected individuals on cART. Predictors of robust Th1 responses to IIV include CD8(+) cell numbers, T cell functionality, and circulating Breg and Treg.
我们研究了接受联合抗逆转录病毒疗法（cART）的HIV感染孕妇对pH1N1单价流感疫苗（IIV1）的Th1保护性及调节性T和B细胞（Treg和Breg）反应。52名研究参与者的外周血单核细胞（PBMC）在接种疫苗前后进行了冷冻保存，并通过流式细胞术进行分析。在用pH1N1和对照抗原进行体外刺激后，检测PBMC中pH1N1特异性Th1、Treg和Breg反应。队列分析未检测到接种疫苗后pH1N1-Th1、Treg或Breg亚群的变化。然而，个体分析区分出了接种疫苗后产生强烈Th1反应的受试者和未产生强烈反应的受试者。接种疫苗后，高pH1N1-Th1与高pH1N1-Treg和Breg反应相关，这表明低流感效应反应并非由疫苗诱导的过度免疫调节所致。接种疫苗后高pH1N1-Th1反应与基线时高PHA和pH1N1-IFN-γ ELISpot以及循环CD4(+)CD39(+)%和CD8(+)CD39(+)% Treg相关，同时与低CD8(+)细胞数量和CD19(+)FOXP3(+)% Breg相关，但与CD4(+)细胞数量或HIV病毒载量无关。这些数据突出了接受cART的HIV感染个体对疫苗的T细胞反应的异质性。对IIV产生强烈Th1反应的预测指标包括CD8(+)细胞数量、T细胞功能以及循环Breg和Treg。
