title: Post-thymic in vivo proliferation of naive CD4+ T cells constrains the TCR repertoire in healthy human adults.
abstract: In spite of thymic involution early in life, the numbers of naive CD4(+) T cells only slowly decline in ageing humans implying peripheral post-thymic naive CD4(+) T cell expansion. This proliferation may compensate for continuous activation and death of naive CD4(+) T cells but may also have negative consequences for protective immunity. Here we show that naive CD4(+) T cells that have proliferated in the periphery are characterized by a highly restricted oligoclonal TCR repertoire. Additionally these cells, which constitute the majority of naive CD4(+) T cells in the elderly, display signatures of recent TCR engagement. Our results demonstrate for the first time that peripheral post-thymic proliferation of naive CD4(+) T cells in healthy human individuals causes a significant contraction of the peripheral TCR repertoire. This age-dependent deterioration of CD4(+) T cell immunity could entail ageing-associated autoimmunity, increased susceptibility to infection or cancer and decreased efficiency of vaccination.
authors.affiliation: German Rheumatism Research Centre, Clinical Immunology, Berlin, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kohler
authors.forename: Ulf
authors.initials: U
authors.lastname: Wagner
authors.forename: Matthias
authors.initials: M
authors.lastname: Pierer
authors.forename: Sonja
authors.initials: S
authors.lastname: Kimmig
authors.forename: Birgit
authors.initials: B
authors.lastname: Oppmann
authors.forename: Beate
authors.initials: B
authors.lastname: Möwes
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jülke
authors.forename: Chiara
authors.initials: C
authors.lastname: Romagnani
authors.forename: Andreas
authors.initials: A
authors.lastname: Thiel
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology*; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D016207:Cytokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens