Post-thymic in vivo proliferation of naive CD4+ T cells constrains the TCR repertoire in healthy human adults.
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.
Kohler
Siegfried
S
German Rheumatism Research Centre, Clinical Immunology, Berlin, Germany.
Wagner
Ulf
U
Pierer
Matthias
M
Kimmig
Sonja
S
Oppmann
Birgit
B
Möwes
Beate
B
Jülke
Kerstin
K
Romagnani
Chiara
C
Thiel
Andreas
A
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*
D016207:Cytokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens