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Early Antigen-Specific Response by Naive CD8 T Cells Is Not Altered with Aging¹

Shaokang P. Li^*, Zeling Cai, Weixing Shi, Anders Brunmark, Michael Jackson and Phyllis-Jean Linton^2,*

^* Sidney Kimmel Cancer Center and R. W. Johnson Pharmaceutical Research Institute, San Diego, CA 92121

Both a dramatic decline in CD8 responses and a switch to memory T cell predominance occur with aging. The extent to which the loss of responsiveness is the consequence of the accumulation of more differentiated vs intrinsically defective T cells (or both) has been unclear. Using similar conditions of Ag stimulation, we have examined the responses generated by CD8⁺ cells isolated from aged TCR transgenic mice. We found that the naive transgene⁺ CD8⁺ cells from aged 2C mice expressed activation markers, produced IL-2, proliferated, and differentiated into cytotoxic T cells as efficiently as their young counterparts. The extent of responsiveness and the level of the responses were comparable in both age groups regardless of the stimulatory conditions used, i.e., partial costimulation/adhesion molecule expression on APCs, or presentation of lower affinity peptide or diminished peptide concentrations. By day 4 after Ag stimulation, no significant age-related differences were observed in the number of effector cells generated nor in the levels of secreted IL-2 or IFN-. Upon restimulation of effector cells, IL-2 secretion and to a lesser extent TNF- expression, but not IFN- secretion, were diminished with age. These findings suggest that age-associated alterations in naive CD8 cell function are not found after primary stimulation, but may become apparent upon restimulation.

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