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- Lyse A. Norian
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
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- Paul M. Allen
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
説明
<jats:title>Abstract</jats:title> <jats:p>Aging is associated with a decline in immune function, particularly within the T cell compartment. Because CD8+ T cells are critical mediators of protective immunity against cancer, which arises more frequently with advancing age, it is important to understand how aging affects T cell-based antitumor responses. We used our DUC18 T cell/CMS5 tumor model system to examine the ability of both aged APCs and aged, tumor-specific CD8+ T cells to mount protective responses to tumors in vivo. An assessment of aged DUC18 T cells in vitro showed a naive phenotype, but impaired proliferation in response to anti-CD3 and anti-CD28 stimulation. We found that DCs from young and old recipient mice are comparable phenotypically, and endogenous APCs in these mice are equally able to prime adoptively transferred young DUC18 T cells. Even when aged DUC18 T cells are transferred into aged CMS5-challenged mice, Ag-specific proliferation and CD25 expression are similar to those found when young DUC18 T cells are transferred into young mice. Although trafficking to tumor sites appears unequal, old and young DUC18 T cells reject primary CMS5 challenges to the same degree and with similar kinetics. Overall, we found no loss of endogenous APC function or intrinsic defects in CD8+ DUC18 T cells with advanced age. Therefore, when young and old tumor-specific T cell populations are equivalently sized, CD8+ T cell-mediated antitumor immunity in our system is not impaired by age, a finding that has positive implications for T cell-based immunotherapies.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 173 (2), 835-844, 2004-07-15
The American Association of Immunologists