Regulatory T cells constrain T cells of shared specificity to enforce tolerance during infection

• 成果类型: Article
• 署名作者: Klawon, David E. J.; Pagane, Nicole; Walker, Matthew T.; Ganci, Nicole K.; Miller, Christine H.; Gai, Eric; Rodriguez, Donald M.; Ryan-Payseur, Bridgett K.; Duncombe, Ryan K.; Adams, Erin J.; Maienschein-Cline, Mark; Freitag, Nancy E.; Germain, Ronald N.; Wong, Harikesh S.; Savage, Peter A.
• 署名单位: University of Chicago; Massachusetts Institute of Technology (MIT); University of Chicago; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Chicago; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Massachusetts Institute of Technology (MIT)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10911
• DOI: 10.1126/science.adk3248
• 发表日期: 2025-03-21
• 关键词: listeria-monocytogenes; negative selection; bacterial pathogenesis; immune homeostasis; molecular mimicry; self-peptide; repertoire; mechanisms; expression; antigen

摘要

During infections, CD4(+) Foxp3(+) regulatory T (T-reg) cells must control autoreactive CD4(+) conventional T (T-conv) cell responses against self-peptide antigens while permitting those against pathogen-derived nonself peptides. We defined the basis of this selectivity using mice in which T-reg cells reactive to a single prostate-specific self-peptide were selectively depleted. We found that self-peptide-specific T-reg cells were dispensable for the control of T-conv cells of matched specificity at homeostasis. However, they were required to control such T-conv cells and prevent autoimmunity toward the prostate after exposure to elevated self-peptide during infection. Notably, the T-reg cell response to self-peptide did not affect protective T-conv cell responses to a pathogen-derived peptide. Thus, self-peptide-specific T-reg cells promoted self-nonself discrimination during infection by selectively controlling T-conv cells of shared self-specificity.