Transient regulatory T cell manipulation is limited by anti-antibody responses in HIV-1 envelope immunized rhesus macaques
Shuqin Gu, Kan Luo, Tarra A. Von Holle, Thaddeus C. Gurley, Hilary Bouton-Verville, Laura L. Sutherland, Robert Parks, Xiaoying Shen, Rachel L. Spreng, Georgia D. Tomaras, David C. Montefiori, Hua-Xin Liao, Barton F. Haynes, M. Anthony Moody
TL;DR
Disrupting regulatory T cells in monkeys with HIV vaccines briefly changes immune responses but is limited by immune reactions to the treatment itself.
Contribution
Demonstrates that anti-CD25 treatment transiently affects Treg cells but is limited by anti-drug antibodies in HIV-vaccinated monkeys.
Findings
Anti-CD25 treatment reduces Treg and follicular Treg cell frequency after the first infusion.
Treg disruption modifies germinal center responses but does not improve antibody breadth.
Anti-drug antibodies develop in treated monkeys, limiting the effectiveness of subsequent infusions.
Abstract
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…
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Taxonomy
TopicsT-cell and B-cell Immunology · HIV Research and Treatment · Immune Cell Function and Interaction