Aged mice exhibit in vivo defective peripheral clonal deletion of D-b/H-Y reactive CD8(+) T cells

We previously reported that T cells from aged mice were resistant to activa tion-induced cell death (AICD) in vitro. To determine whether the presence of AICD-resistant T cells is associated with defects in age-related periphe ral clonal deletion in vivo, congenic male SCID mice were reconstituted wit h T cells from aged or young female D-b/H-Y TCR (Tg71) transgenic mice. Com pared with recipients of young cells, the recipients of T cells from aged m ice exhibited a 3-fold increase in the percentage of autoreactive CD8(+) H- Y antigen-reactive T cells as defined by the clonotypic antibody, M33. Ther e were significantly increased sera levels of interferon-gamma, a significa ntly decreased expression of FasL by M33(+)CD8(+) T cells, and significantl y decreased apoptosis by DNA fragmentation staining of the spleen of mice r econstituted with T cells from aged mice compared to those from young mice. By day 21, the recipients of T cells from aged mice but not young mice, ex hibited infiltration of CD3(+) cells into the non-lymphoid organs. These re sults indicate that there is defective peripheral deletion of the self-reac tive T cells derived from aged female Tg71 mice, and that failure to delete these cells is associated with the defective T-cell clonal deletion in the recipient mice. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved .