Gu Shuqin, Luo Kan, Von Holle Tarra A, Gurley Thaddeus C, Bouton-Verville Hilary, Sutherland Laura L, Parks Robert, Shen Xiaoying, Spreng Rachel L, Tomaras Georgia D, Montefiori David C, Liao Hua-Xin, Haynes Barton F, Moody M Anthony
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
iScience. 2025 Jul 23;28(8):113191. doi: 10.1016/j.isci.2025.113191. eCollection 2025 Aug 15.
CD25 FoxP3 CD4 regulatory T (Treg) cells promote immune tolerance. We studied germinal center responses and HIV-1 antibody development in rhesus macaques (RMs) immunized with sequential CH505 gp120 envelopes (Envs), with or without anti-CD25 monoclonal antibody (mAb). Plasma Env antibody levels and CD4 binding sited-directed responses were similar across groups. Treg and CXCR5-expressing follicular Treg cell frequency dropped more than two times after the first anti-CD25 infusion but not later ones. Transient Treg disruption was associated with a reduced proportion of vaccine-elicited B cell clonal lineages in lymphoid tissue, but did not result in neutralization breadth. Anti-CD25-treated RMs developed anti-drug antibodies, correlating with reduced plasma mAb levels after subsequent infusions. Germinal center responses were modified by Treg perturbation intended to induce HIV-1 bnAbs, but this effect was curtailed by anti-antibody responses. This may have implications for vaccination in persons receiving immune modulating drugs for transplants or other medical conditions.
CD25 FoxP3 CD4调节性T（Treg）细胞促进免疫耐受。我们研究了用连续的CH505 gp120包膜（Env）免疫的恒河猴（RM）的生发中心反应和HIV-1抗体产生情况，免疫时使用或不使用抗CD25单克隆抗体（mAb）。各组间血浆Env抗体水平和CD4结合位点定向反应相似。在首次输注抗CD25后，Treg和表达CXCR5的滤泡性Treg细胞频率下降超过两倍，但后续输注后未出现这种情况。短暂的Treg破坏与淋巴组织中疫苗诱导的B细胞克隆谱系比例降低有关，但未导致中和广度增加。接受抗CD25治疗的RM产生了抗药物抗体，这与后续输注后血浆mAb水平降低相关。旨在诱导HIV-1 bnAb的Treg扰动改变了生发中心反应，但这种效应被抗抗体反应所抑制。这可能对接受免疫调节药物进行移植或其他医疗状况的人群的疫苗接种有影响。
