title: Subsets of nonclonal neighboring CD4+ T cells specifically regulate the frequency of individual antigen-reactive T cells.
abstract: After an immune response, the expanded population of antigen-specific CD4(+) T cells contract to steady state levels. We have found that the contraction is neither cell-autonomous nor mediated by competition for generic trophic factors, but regulated by relatively rare subsets of neighboring CD4(+) T cells not necessarily of a conventional regulatory T cell lineage. These regulators, referred to as deletors, specifically limit the frequency of particular antigen-specific T cells even though they are not reactive to the same agonist as their targets. Instead, an isolated deletor could outcompete the target for recognition of a shared, nonstimulatory endogenous peptide-MHC ligand. This mechanism was sufficient to prevent even agonist-driven autoimmune disease in a lymphopenic environment. Such a targeted regulation of homeostasis within narrow colonies of T cells with related TCR specificities for subthreshold ligands might help to prevent the loss of unrelated TCRs during multiple responses, preserving the valuable diversity of the repertoire.
authors.affiliation: Laboratory of Cellular and Molecular Immunology, NIAID, NIH, Bethesda, MD 20892, USA. ns117r@nih.gov
authors.forename: Nevil J
authors.initials: NJ
authors.lastname: Singh
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Bando
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D008024:Ligands; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity
chemical_list: D000941:Antigens; D008024:Ligands; D011948:Receptors, Antigen, T-Cell