| First Author | Messaoudi I | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 1 | Pages | 301-8 |
| PubMed ID | 16365422 | Mgi Jnum | J:126270 |
| Mgi Id | MGI:3760933 | Doi | 10.4049/jimmunol.176.1.301 |
| Citation | Messaoudi I, et al. (2006) Molecular, cellular, and antigen requirements for development of age-associated T cell clonal expansions in vivo. J Immunol 176(1):301-8 |
| abstractText | 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 CD8 T cell turnover and an accumulation of memory-phenotype T cells. These data suggested that homeostatic cell division in the CD8 compartment enhances the formation of TCE. Repeated immunization with peptide/adjuvant did not result in an increase in Ag-specific 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. |
