GENETIC-CONTROL OF IMMUNE RESPONSIVENESS, AGING AND TUMOR-INCIDENCE

Age-related alterations of the immune system affect both antibody and cell-mediated immune responses, T-cell responses being more severely a ffected than B-cell responses. Within the T-cell population, aging lea ds to replacement of virgin by memory cells and to accumulation of cel ls with signal transduction defects. Changes in T-cell subsets and in cytokine production profiles may produce suitable conditions for T-cel l-mediated disregulation of antibody responses characterized by the pr oduction of low affinity and self-reactive antibodies. Also B-cells ex hibit intrinsic defects and natural killer (NK) cell activity a profou nd loss in old mice. Whether age-related immune disfunctions influence life span and tumor incidence has been examined in mice genetically s elected for high or low antibody responsiveness. It has been found tha t genetic selection of vigorous antibody responses in most cases produ ces mice with longer life span and lower lymphoma incidence. Moreover, the results of genetic segregation experiments indicate that antibody responsiveness and life span are polygenic traits regulated by a smal l number of the same or closely linked loci. Mice genetically selected for high or low mitotic responsiveness to PHA exhibit low or high tum or incidence, respectively, but no difference in life span, suggesting that T-cell activity is restricted to immune surveillance of neoplast ic transformation. Studies on mice genetically selected for resistance or sensitivity to chemical carcinogenesis have uncover-ed loci that c ontrol both resistance to tumor induction and longevity while have no effects on immunity and disease incidence. Thus, the relative role of the immune system in conditioning the duration and the biological qual ity of life remains to be determined. (C) 1997 Elsevier Science Irelan d Ltd.