School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia.
Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Perth, WA, Australia.
Front Immunol. 2019 Apr 24;10:839. doi: 10.3389/fimmu.2019.00839. eCollection 2019.
Greater understanding of factors influencing the maturation of antibody responses against pneumococcal polysaccharides (PcPs) may improve pneumococcal vaccination strategies. Although PcPs are type 2 T cell-independent antigens thought not to induce follicular immune responses, we have previously shown that IgG2 antibody responses against antigens in the 23-valent unconjugated PcP vaccine (PPV23) are associated with expansion of ICOS circulating T follicular helper (cT) cells in HIV seronegative subjects but not HIV patients. As IL-7Rα signaling in CD4 T cells may affect T cell function and is adversely affected by HIV-1 infection, we have examined the relationship of IL-7Rα expression on ICOS cT cells with PcP-specific IgG2 antibody responses. PPV23 vaccination was undertaken in HIV patients receiving antiretroviral therapy ( = 25) and HIV seronegative subjects ( = 20). IL-7Rα expression on ICOS and ICOS cT cells was assessed at day(D) 0, 7, and 28. Fold increase between D0 and D28 in serum IgG1 and IgG2 antibodies to PcP serotypes 4, 6B, 9V, and 14 and the frequency of IgG1 and IgG2 antibody secreting cells (ASCs) at D7 were also assessed. Decline in IL-7Rα expression on ICOS cT cells between D0 and D7 occurred in 75% of HIV seronegative subjects and 60% of HIV patients (Group A), with changes in IL-7Rα expression being more pronounced in HIV patients. Group A patients exhibited abnormally high IL-7Rα expression pre-vaccination, an association of serum IgG2, but not IgG1, antibody responses with a decline of IL-7Rα expression on ICOS cT cells between D0 and D7, and an association of higher IgG2 ASCs with lower IL-7Rα expression on ICOS cT cells at D7. As decline of IL-7Rα expression on CD4 T cells is an indicator of IL-7Rα signaling, our findings suggest that utilization of IL-7 by cT cells affects production of IgG2 antibodies to PPV23 antigens in some HIV patients.
对影响肺炎球菌多糖（PcP）抗体成熟的因素有更深入的了解，可能会改善肺炎球菌疫苗接种策略。虽然 PcP 是 2 型 T 细胞非依赖性抗原，被认为不会诱导滤泡免疫反应，但我们之前已经表明，针对 23 价未结合肺炎球菌多糖疫苗（PPV23）中抗原的 IgG2 抗体反应与 HIV 血清阴性受试者而非 HIV 患者中 ICOS 循环滤泡辅助 T 细胞（cT）的扩增有关。由于 CD4 T 细胞中的 IL-7Rα 信号可能会影响 T 细胞功能，并且会受到 HIV-1 感染的不利影响，因此我们检查了 ICOS cT 细胞上的 IL-7Rα 表达与 PcP 特异性 IgG2 抗体反应之间的关系。在接受抗逆转录病毒治疗的 HIV 患者（n=25）和 HIV 血清阴性受试者（n=20）中进行了 PPV23 疫苗接种。在 0、7 和 28 天评估了 ICOS 和 ICOS cT 细胞上的 IL-7Rα 表达。还评估了血清 IgG1 和 IgG2 抗体对 PcP 血清型 4、6B、9V 和 14 的反应在 D0 至 D28 之间的倍数增加以及 D7 时 IgG1 和 IgG2 抗体分泌细胞（ASC）的频率。在 75%的 HIV 血清阴性受试者和 60%的 HIV 患者（A 组）中，在 D0 和 D7 之间 ICOS cT 细胞上的 IL-7Rα 表达下降，而在 HIV 患者中这种变化更为明显。A 组患者在接种疫苗前表现出异常高的 IL-7Rα 表达，血清 IgG2 但不是 IgG1 抗体反应与 D0 和 D7 之间 ICOS cT 细胞上 IL-7Rα 表达的下降有关，并且 D7 时更高的 IgG2 ASC 与 ICOS cT 细胞上更低的 IL-7Rα 表达有关。由于 CD4 T 细胞上 IL-7Rα 表达的下降是 IL-7Rα 信号的一个指标，我们的发现表明，cT 细胞对 IL-7 的利用会影响一些 HIV 患者对 PPV23 抗原的 IgG2 抗体的产生。
