Age-associated decline in precursor frequency for different T cell-mediated reactions, with preservation of helper or cytotoxic effect per precursor cell.

We have begun to apply limiting dilution methods to address the cellular interactions that underlie age-associated changes in the immune response. By 18 mo of age, mice of the long-lived (BALB/c X C57BL/6)F1 strain are found to have a consistent, three to fivefold decline in precursor frequency for several different T cell-mediated responses: a) IL 2 response to T cell mitogens; b) antigen-nonspecific CTL production in mitogen-stimulated, IL 2-supplemented responses; and c) proliferation in response to concanavalin A. We also find a diminished precursor frequency for IL 2-secreting, KLH-specific helper T cells in the draining lymph nodes of KLH-immunized mice. Despite the decline in the fraction of responding precursor cells, the amount of "effect" (cytotoxicity, IL 2, or proliferation) generated per responsive cell is not altered by age. We speculate that the decline in all of these assays may reflect a common, underlying defect, one that reduces the proportion of T cells that can generate a sizeable clone of proliferating cells. This defect seems to act in several different T cell subsets, and in responses to several activating stimuli: alloantigens, soluble proteins, or mitogens.