ASSESSMENT OF ALLOREACTIVE T-CELL SUBPOPULATIONS OF AGED MICE IN-VIVO- CD4-CELL-MEDIATED REJECTION RESPONSE DECLINES WITH ADVANCED AGE( BUT NOT CD8+ T)

The present investigation explored age-related alterations in T cell p opulations mediating allospecific responses in vivo. Healthy aged and young H-2(b) and H-2(b)xH-2(k) mice were engrafted with major histocom patibility complex (MHC) class II-disparate bm12 skin, rejection of wh ich requires CD4(+) T cells, and MHC class I-disparate bm1 skin, rejec tion of which requires CD8(+) T cells. Aged mice of both genders exhib ited prolonged survival of bm12 skin grafts relative to their young co unterparts but rejected bm1 skin grafts at a rate equivalent to that o f young mice. Consistent with prolonged survival of bm12 skin grafts, markedly diminished levels of Ia(bm12) CTL activity were elicited from T cells of aged mice in vitro. However, no such decline was observed in the level of K-bm1 CTL from T cells of aged mice. The alterations i n Ia(bm12) allospecific responses were not attributable to quantitativ e changes in CD4(+) T cells of aged mice, and addition of soluble T ce ll helper factors to response cultures of aged mice did not augment Ia (bm12) cytotoxic T lymphocytes activity These data demonstrate that ag ing fundamentally affects CD4(+) T cell-mediated allospecific response s particularly in vivo, and that deficient generation of soluble T cel l helper factors alone cannot explain this deficit.