The turnover of subsets of T cells in young and aged mice will be examined under various conditions by administering the DNA precursor, bromodeoxyuridine (BrdU), in the drinking water and then staining T cells for BrdU incorporation vs the expression of various surface markers. Studies on young mice have shown that T cells with a naive (CD44/lo) phenotype have a much slower turnover than memory-phenotype (CD44/hi) cells; comparable information will be sought on aged (2-year-old) mice. The possibility that T cell proliferation in vivo is mediated largely by cytokines released during infection with pathogens will be explored. Preliminary work has established that viral infections in young mice induce intense proliferation of CD44/hi CD8+ cells and that proliferation of these cells can be mimicked by injection of type I interferon (IFN I) and by IFN I-inducers such as Poly I:C. These findings suggest that production of certain cytokines, notably IFN I, during viral infection cause TCR-independent """"""""bystander"""""""" stimulation of T cells. The range of cytokines contributing to bystander proliferation of T cells is unknown and will be tested by injecting young and old mice with a range of different cytokines and then examining proliferation of T cell subsets. The possibility that cytokines contribute to the generation and survival of antigen-specific memory cells will be examined by priming TCR transgenic T cells to antigen in the presence of IFN I and then studying the fate of the responding T cells.
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| 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 |
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| 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 |
| Ishimaru, Naozumi; Kishimoto, Hidehiro; Hayashi, Yoshio et al. (2006) Regulation of naive T cell function by the NF-kappaB2 pathway. Nat Immunol 7:763-72 |
| 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 |
| Kovar, Marek; Boyman, Onur; Shen, Xuefei et al. (2006) Direct stimulation of T cells by membrane vesicles from antigen-presenting cells. Proc Natl Acad Sci U S A 103:11671-6 |
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