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

✍ Scribed by Siegfried Kohler; Ulf Wagner; Matthias Pierer; Sonja Kimmig; Birgit Oppmann; Beate Möwes; Kerstin Jülke; Chiara Romagnani; Andreas Thiel

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 243 KB
• Volume: 35
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200526181

✦ Synopsis

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.