Factors involved in the nonspecific and specific proliferative responses of T cells were examined in the A/J strain of mice that were physiologically aged in the specific pathogen-free condition. In aged A/J mice, the production of IL-1 and IL-2 from optimally stimulated peritoneal macrophages and splenic T cells was significantly decreased, while the production of IL-3 by T cells was increased. T cells from old mice showed a higher threshold for concanavalin A stimulation for the induction of IL-2 receptors. The same T cells responded only slightly in the mixed lymphocyte reaction (MLR) stimulated by allogeneic class II antigens, while they showed a high background stimulation without stimulators. The addition of syngeneic accessory cells did not increase the proliferative response of T cells from aged animals. T cells from bone marrow chimeras constituted by transferring stem cells from young A/J into irradiated old B10.A mice (young A/J → old B10.A chimeras) showed a pattern very similar to that of old A/J T cells, whereas those from the old A/J → young B10.A chimeras exhibited a response pattern comparable to that of normal young A/J cells. These results indicated that the proliferative responses in aged animals are abnormal, partially due to the alterations in the interleukin cascade. Some changes are probably due to the effect of environment where T cells undergo early differentiation, because bone marrow stem cells from aged mice can generate T cells with normal functions when differentiated in the young environm
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