Aging is associated with a decline in the repertoire and the functional capacity of the mature T cells. The reduced ability of the aged cellular immune system to respond to new antigenic challenges appears to be largely a result of attrition in the size of the naive T cell pool and the decline in the responsiveness of the antigen-specific T cells. Exactly what causes the reduction of the naive T cell pool is not known, but is generally believed to be a combination of decreased thymic output of newly generated T cells coupled with life-long conversion of naive cells into memory cells from exposure to antigens. Other mechanisms, however, are possible, especially when one considers that T cells are subject to constant regulation by homeostatic mechanisms that regulate the overall size and the composition of the T cell pool. In this respect, we and others have recently begun to identify the essential factors that regulate the homeostasis of naive and memory T cells. To determine whether the decline in the naive cells in the aged is partly caused by age-related changes in the factors that control T cell homeostasis, we propose following three areas of investigation. First, the host environment of the aged will be tested for their capacity to support homeostasis of naive and memory T cells. Second, the expression of factors that regulate homeostasis of naive T cells will be measured in aged mice. Third, the possibility of restoring the naive T cell pool in old mice through manipulation of the homeostatic factors will be tested.
| Becklund, Bryan R; Purton, Jared F; Ramsey, Chris et al. (2016) The aged lymphoid tissue environment fails to support naïve T cell homeostasis. Sci Rep 6:30842 |
| Boyman, Onur; Ramsey, Chris; Kim, David M et al. (2008) IL-7/anti-IL-7 mAb complexes restore T cell development and induce homeostatic T Cell expansion without lymphopenia. J Immunol 180:7265-75 |
| Ramsey, Chris; Rubinstein, Mark P; Kim, David M et al. (2008) The lymphopenic environment of CD132 (common gamma-chain)-deficient hosts elicits rapid homeostatic proliferation of naive T cells via IL-15. J Immunol 180:5320-6 |
| Purton, Jared F; Sprent, Jonathan; Surh, Charles D (2007) Staying alive--naive CD4(+) T cell homeostasis. Eur J Immunol 37:2367-9 |
| Purton, Jared F; Tan, Joyce T; Rubinstein, Mark P et al. (2007) Antiviral CD4+ memory T cells are IL-15 dependent. J Exp Med 204:951-61 |
| Rubinstein, Mark P; Kovar, Marek; Purton, Jared F et al. (2006) Converting IL-15 to a superagonist by binding to soluble IL-15R{alpha}. Proc Natl Acad Sci U S A 103:9166-71 |
| Boyman, Onur; Cho, Jae-Ho; Tan, Joyce T et al. (2006) A major histocompatibility complex class I-dependent subset of memory phenotype CD8+ cells. J Exp Med 203:1817-25 |
| Surh, Charles D; Boyman, Onur; Purton, Jared F et al. (2006) Homeostasis of memory T cells. Immunol Rev 211:154-63 |
| Davey, Gayle M; Starr, Robyn; Cornish, Ann L et al. (2005) SOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential. J Exp Med 202:1099-108 |
| Surh, Charles D; Sprent, Jonathan (2005) Regulation of mature T cell homeostasis. Semin Immunol 17:183-91 |
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