title: Weakly self-reactive T-cell clones can homeostatically expand when present at low numbers.
abstract: T-cell division is central to maintaining a stable T-cell pool in adults. It also enables T-cell expansion in neonates, and after depletion by chemotherapy, bone marrow transplantation, or infection. The same signals required for T-cell survival in lymphoreplete settings, IL-7 and T-cell receptor (TCR) interactions with self-peptide MHC (pMHC), induce division when T-cell numbers are low. The strength of reactivity for self-pMHC has been shown to correlate with the capacity of T cells to undergo lymphopenia-induced proliferation (LIP), in that weakly self-reactive T cells are unable to divide, implying that T-cell reconstitution would significantly skew the TCR repertoire toward TCRs with greater self-reactivity and thus compromise T-cell diversity. Here, we show that while CD4+T cells with low self-pMHC reactivity experience more intense competition, they are able to divide when present at low enough cell numbers. Thus, at physiological precursor frequencies CD4+T cells with low self-pMHC reactivity are able to contribute to the reconstitution of the T-cell pool.
authors: Department of Respiratory Medicine, Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Nienke
authors: N
authors: Vrisekoop
authors: Department of Physiology, Complex Traits Group, McGill University, Montreal, Quebec, Canada.
authors: Patricio
authors: P
authors: Artusa
authors: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Joao P
authors: JP
authors: Monteiro
authors: Department of Physiology, Complex Traits Group, McGill University, Montreal, Quebec, Canada.
authors: Judith N
authors: JN
authors: Mandl
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015551:Autoimmunity; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002999:Clone Cells; D015870:Gene Expression; D006706:Homeostasis; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D011948:Receptors, Antigen, T-Cell
keywords: Lymphopenia-induced proliferation; Regulation of homeostasis; T-cell competition; T-cell diversity; T-cell repertoire