Aging and autoimmune disorders are often associated and share certain immune abnormalities suggesting common or related underlying defects.
The aim of this proposal is to determine the causes for longevity in murine models for systemic autoimmune diseases with particular emphasis on the mechanisms responsible for the occurrence of sporadic long-lived individuals (approximately 4 times expected life span) in otherwise early- dying MRL-1pr/1pr and male BXSB lupus mice. To this end, we will determine whether longevity in these mice has genetic causes which would allow us to establish long-lived, coisogenic sublines carrying the mutated gene, or results from environmental factors or random somatic events. In the latter, attempts will be performed to clarify the molecular nature of the respective factors and events. To establish whether long-lived mice develop autoimmune symptoms and/or disease, serologic, pathologic, and histopathologic parameters associated with longevity will be established and compared with those from short- lived mice, and from the late-life lupus strains MRL-+/+ and female BXSB. Finally, because of the involvement of endogenous murine retroviruses in lupus-associated immune responses, certain lymphoproliferative disorders, and mutagenesis, we will investigate whether longevity is associated with or caused by differential retroviral insertion into germline or somatic DNA and/or results from differences in retroviral gene expression.
| 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 |
| Jelley-Gibbs, Dawn M; Strutt, Tara M; McKinstry, K Kai et al. (2008) Influencing the fates of CD4 T cells on the path to memory: lessons from influenza. Immunol Cell Biol 86:343-52 |
| 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 |
| 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 |
| Haynes, Laura; Eaton, Sheri M; Burns, Eve M et al. (2005) Newly generated CD4 T cells in aged animals do not exhibit age-related defects in response to antigen. J Exp Med 201:845-51 |
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