T cell development and receptor diversity during aging

Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalReview articlepeer-review

201 Scopus citations

Abstract

The T cell system is a complex and highly dynamic system that is amazingly robust over many decades of human life. Its functional competence is determined not only by its size but also by its diversity. Homeostatic control mechanisms have to secure sufficient T cell replenishment while preventing loss of clonal diversity. Major homeostatic challenges include profound expansion and shrinkage of T cell clonotypes upon antigenic triggering and, more importantly, age-related changes in T cell regeneration. The ability of the thymus to rebuild a diverse repertoire ceases in the fifth decade of life. Emerging data suggest that the end of the 7th decade of life defines a critical time period when T cell homeostasis is no longer guaranteed and diversity of the naïve T-cell repertoire collapses. Thus, failure of T cell homeostasis appears to result from cumulative defects of T cell generation. Elucidation of the underlying mechanisms will allow for extending this turning point to later in life; ultimately, interventions have to aim at restoring thymic function and complementary modes of T cell reconstitution.

Original languageEnglish (US)
Pages (from-to)468-475
Number of pages8
JournalCurrent Opinion in Immunology
Volume17
Issue number5
DOIs
StatePublished - Oct 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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