Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 58:B1063-B1073 (2003)
© 2003 The Gerontological Society of America

Antigen-Independent Expansion of CD28hi CD8 Cells From Aged Mice: Cytokine Requirements and Signal Transduction Pathways

Anavelys Ortiz-Suárez1 and Richard A. Miller1,2,3

1 Cellular and Molecular Biology Graduate Program
2 Department of Pathology, University of Michigan School of Medicine, Ann Arbor.
3 University of Michigan Geriatrics Center, and VA Medical Center, Ann Arbor, Michigan.

Memory CD8+ T cells from old mice can proliferate in nonirradiated recipients. Transfer of labeled cells from aged donors into young recipients showed that proliferation of aged donor CD8 cells requires host cells that can both respond to interferon-{gamma} and produce interleukin-15. Reisolation of transferred CD8 cells from host mice showed that LAT (linker for activated T cells) translocation to the immunological synapse, and translocation of NF (nuclear factor)-{kappa}B to the nucleus were diminished in recovered CD8 T cells from old donors, whether they had divided in vivo or not. Cells able to proliferate in vivo could be isolated based on their unusually high levels of CD28 expression, but were found not to differ from other aged CD8 cells in their low levels of LAT and protein kinase C-theta (PKC-{theta}) translocation to the immunological synapse. Thus in vivo proliferation of CD28hi CD8 cells from aged mice cannot be attributed to retention of T-cell receptor signaling.







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