Alloreactive cytotoxic T lymphocytes from aged mice express increased lysis of autologous and third-party target cells.

Abstract

Much data support the notion that with increasing age a decline in T cell effector function occurs. In the present study, qualitative rather than quantitative age-related changes in vitro alloreactive cytotoxic T lymphocyte (CTL) responses were observed. The level of specific alloreactive CTL responses was not consistently lower in aged mice, although some displayed a somewhat lower response. A more striking feature, however, was that alloimmune CTL from old mice lyse 'third party,' TNP-modified syngeneic and unmodified syngeneic target cells to a significantly greater extent than do alloreactive CTL from young mice. In fact, alloreactive CTL from young mice do not lyse unmodified autologous target cells at all. The lysis of 'third party' and autologous target cells by CTL generated in response to allogeneic stimulator cells is truly cross-reactive, since it can be specifically blocked by the relevant cold (not 51Cr-labeled) target cells as well as by cold target cells of the original stimulator cell type. Different subsets of alloreactive CTL from old mice are involved in 'third party' and autologous target cell lysis, since cold autologous blocking cells cannot block lysis of 'third party' target cells and vice versa. The reasons for the increased cross-reactivity of alloreactive CTL from old mice are not clear. We hypothesize that either a decline in suppressor cells or prolonged exposure to autologous MHC determinants modified by natural pathogens might be involved in the generation of the spectrum of cross-reactivities described here. Chemicals/CAS: Epitopes; Isoantigens; Trinitrobenzenes