Decline, in aging mice, of the anti‐2, 4, 6‐trinitrophenyl (TNP) cytotoxic T cell response attributable to loss of Lyt‐2−, interleukin 2‐producing helper cell function

摘要

AbstractThein vitrogeneration of cytotoxic T lymphocytes (CTL) specific for 2, 4, 6‐trinitrophenyl (TNP)‐modified syngeneic spleen cells is found to be almost invariably depressed in apparently healthy 18‐month‐old mice of the long‐lived (BALB/c × C57BL/6)F1hybrid strain. Studies of CTL production from Lyt‐2+thymus cells have suggested that pre‐killer cells may require, for maturation into effectors, the presence of a soluble helper factor, interleukin 2 (IL2), produced by Lyt‐2−cells which are themselves devoid of pre‐CTL activity. We have therefore developed a petri‐dish adherence technique for separating spleen cells into Lyt‐2+and Lyt‐2−populations in order to test for helper and pre‐killer activity independently. Pre‐CTL function is measured by stimulating Lyt‐2+cells in the presence of exogenous IL2. Helper cell activity is tested by adding Lyt‐2−cells to “indicator” populations of Lyt‐2+pre‐CTL. Estimation of IL2 levels in medium conditioned by unfractionated, TNP‐self‐stimulated splenocytes provides a second measurement of helper cell function.Mice 18 months of age, when compared to 4 month‐old controls, are found to retain nearly all of their pre‐CTL activity, but to have lost sufficient helper cell activity to account for the decline in unseparated spleen c