Adoptive transfer of transgenic Tconv cells against the prostate self-peptide C4 did not induce autoimmunity and prompted polyclonal Treg accumulation around Tconv. Infection with a C4-expressing virus also did not break tolerance, however, C4-specific Tregs colocalized significantly with Tconv in this setting. Deletion of C4-specific Tregs resulted in significant prostatic autoimmunity and enrichment of proliferative and SCM-like T cell clusters. Analysis of Treg/Tconv pairings in WT mice revealed that matched Tregs were required to control a portion of Tconv that escaped polyclonal control, likely accomplished in part by earlier expansion.
Contributed by Morgan Janes
ABSTRACT: During infections, CD4(+) Foxp3(+) regulatory T (Treg) cells must control autoreactive CD4(+) conventional T (Tconv) 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 Treg cells reactive to a single prostate-specific self-peptide were selectively depleted. We found that self-peptide-specific Treg cells were dispensable for the control of Tconv cells of matched specificity at homeostasis. However, they were required to control such Tconv cells and prevent autoimmunity toward the prostate following exposure to elevated self-peptide during infection. Importantly, the Treg cell response to self-peptide did not impact protective Tconv cell responses to a pathogen-derived peptide. Thus, self-peptide-specific Treg cells promoted self-nonself discrimination during infection by selectively controlling Tconv cells of shared self-specificity.
Author Info: (1) Department of Pathology, University of Chicago, Chicago, IL, USA. (2) The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA. Program in Computational and Sys
Author Info: (1) Department of Pathology, University of Chicago, Chicago, IL, USA. (2) The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA. Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. (3) Department of Pathology, University of Chicago, Chicago, IL, USA. (4) Department of Pathology, University of Chicago, Chicago, IL, USA. (5) Department of Pathology, University of Chicago, Chicago, IL, USA. Interdisciplinary Scientist Training Program, University of Chicago, Chicago, IL, USA. (6) The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA. Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. (7) Department of Pathology, University of Chicago, Chicago, IL, USA. Interdisciplinary Scientist Training Program, University of Chicago, Chicago, IL, USA. (8) Department of Microbiology and Immunology, University of Illinois Chicago, Chicago, IL, USA. (9) Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA. (10) Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA. (11) Research Informatics Core, Research Resources Center, University of Illinois Chicago, Chicago, IL, USA. (12) Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL, USA. (13) Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. (14) The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. (15) Department of Pathology, University of Chicago, Chicago, IL, USA.
