Molecular, cellular, and antigen requirements for development of age-associated T cell clonal expansions in vivo

Ilhem Messaoudi, Jessica Warner, Dragana Nikolich-Žugich, Miranda Fischer, Janko Nikolich-Žugich

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

T cell aging manifests itself both at the cellular (cell-autonomous defects in signaling) and at the population (age-related dysregulation of T cell homeostasis) levels. A prominent contributor to the latter is the appearance of T cell clonal expansions (TCE), with a potential to impair immune defense. In this study, we investigated molecular, cellular, and Ag requirements for TCE development. Of the mutant mice tested, old animals lacking MHC class I exhibited 7-fold fewer TCE than controls, with a 7-fold reduction in TCE. By contrast, animals lacking only one of the MHC class I molecules (Kb or Db), or IL-7R, or devoid of T cell renewal via adult thymectomy, all exhibited significant increases in TCE incidence. This increase directly correlated to lymphopenia, increased CDS T cell turnover and an accumulation of memory-phenotype T cells. These data suggested that homeostatic cell division in the CDS compartment enhances the formation of TCE. Repeated immunization with peptide/adjuvant did not result in an increase in Ag-speciflc TCE; however, adjuvant alone increased TCE incidence. In these experiments, therefore, nonspecific and/or homeostatic proliferation was more efficient in generating TCE in mice than repeated Ag-driven stimulation, suggesting that many, if not most, TCE in specific pathogen-free laboratory mice may be Ag-independent.

Original languageEnglish (US)
Pages (from-to)301-308
Number of pages8
JournalJournal of Immunology
Volume176
Issue number1
DOIs
StatePublished - Jan 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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