Subsets of Nonclonal Neighboring CD4+ T Cells Specifically Regulate the Frequency of Individual Antigen-Reactive T Cells

Laboratory of Cellular and Molecular Immunology, NIAID, NIH, Bethesda, MD 20892, USA. Electronic address: .
Immunity (Impact Factor: 21.56). 09/2012; 37(4):735-46. DOI: 10.1016/j.immuni.2012.08.008
Source: PubMed


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.

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    • "In order to explain this stability, concepts have emerged that are based on competition between T cells for limiting trophic resources needed for survival and proliferation (7). The limiting trophic resources can be divided in public and TCR-specific resources (8). In principle, public trophic resources are equally accessible to all T cells, and include stimulatory cytokines (e.g. "
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