U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA; Institute for HIV Research, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
Immunity. 2016 Jan 19;44(1):167-178. doi: 10.1016/j.immuni.2015.12.011. Epub 2016 Jan 12.
A central effort in HIV vaccine development is to generate protective broadly neutralizing antibodies, a process dependent on T follicular helper (Tfh) cells. The feasibility of using peripheral blood counterparts of lymph node Tfh cells to assess the immune response and the influence of viral and vaccine antigens on their helper functions remain obscure. We assessed circulating HIV-specific IL-21(+)CD4(+) T cells and showed transcriptional and phenotypic similarities to lymphoid Tfh cells, and hence representing peripheral Tfh (pTfh) cells. pTfh cells were functionally active and B cell helper quality differed depending on antigen specificity. Furthermore, we found higher frequency of pTfh cells in peripheral blood mononuclear cell specimens from the ALVAC+AIDSVAX (RV144) HIV vaccine trial associated with protective antibody responses compared to the non-protective DNA+Ad5 vaccine trial. Together, we identify IL-21(+)CD4(+) T cells as pTfh cells, implicating them as key populations in the generation of vaccine-evoked antibody responses.
HIV 疫苗研发的核心工作是产生保护性广谱中和抗体，这一过程依赖于滤泡辅助性 T 细胞（Tfh）。利用淋巴结 Tfh 细胞的外周血对应物来评估免疫反应以及病毒和疫苗抗原对其辅助功能的影响的可行性仍然不清楚。我们评估了循环 HIV 特异性 IL-21（+）CD4（+）T 细胞，并显示出与淋巴样 Tfh 细胞的转录和表型相似性，因此代表外周 Tfh（pTfh）细胞。pTfh 细胞具有功能活性，B 细胞辅助质量取决于抗原特异性。此外，我们发现与非保护性 DNA+Ad5 疫苗试验相比，在 ALVAC+AIDSVAX（RV144）HIV 疫苗试验的外周血单核细胞标本中，pTfh 细胞的频率更高，与保护性抗体反应相关。总之，我们将 IL-21（+）CD4（+）T 细胞鉴定为 pTfh 细胞，这表明它们是疫苗诱导的抗体反应产生的关键群体。
