Post-thymic in vivo proliferation of naive CD4+ T cells constrains the TCR repertoire in healthy human adults

Eur J Immunol. 2005 Jun;35(6):1987-94. doi: 10.1002/eji.200526181.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / immunology*
  • Autoimmunity
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / pharmacology
  • Humans
  • Leukocyte Common Antigens / analysis
  • Lymphocyte Activation*
  • Middle Aged
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Receptors, Antigen, T-Cell / physiology*
  • Thymus Gland / immunology*

Substances

  • Cytokines
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, Antigen, T-Cell
  • Leukocyte Common Antigens