Analysis of Age-Related Degeneracy of T-Cell Repertoire: Localized Functional Failure in CD8+ T Cells

The repertoire and frequency of alloreactive T cells in aged mice were examined by limiting dilution analysis of the mixed-lymphocyte reaction (MLR). Mice were aged in specific pathogen-free conditions up to 31 months, and MLR of their spleen cells under limiting dilution conditions was examined at various stages of ageing. The frequency of alloreactive T cells was found to decrease in mice more than 14 months of age, and the value reached about 1/3 of that of young mice of 2 months of age. The slope analysis of cell dose-response curves of MLR indicated the existence of two interacting T-cell populations, i.e. CD4+ and CD8+, cooperation between which is required for the full manifestation of MLR in limiting dilution conditions. The decrease in the alloreactivity of aged spleen cells was ascribed to the selective functional loss of the CD8+ population, because the CD4+ but not the CD8+ T-cell fraction from aged mice could restore the limiting factor in MLR. The decrease in the cooperative activity of CD8+ T cells in allo-MLR starts much earlier than the decrease in the number of CD8+ T cells in the spleen.