title: Genetic control of immune responsiveness, aging and tumor incidence.
abstract: Age-related alterations of the immune system affect both antibody and cell-mediated immune responses, T-cell responses being more severely affected than B-cell responses. Within the T-cell population, aging leads to replacement of virgin by memory cells and to accumulation of cells with signal transduction defects. Changes in T-cell subsets and in cytokine production profiles may produce suitable conditions for T-cell-mediated disregulation of antibody responses characterized by the production of low affinity and self-reactive antibodies. Also B-cells exhibit intrinsic defects and natural killer (NK) cell activity a profound loss in old mice. Whether age-related immune disfunctions influence life span and tumor incidence has been examined in mice genetically selected for high or low antibody responsiveness. It has been found that genetic selection of vigorous antibody responses in most cases produces 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 small number of the same or closely linked loci. Mice genetically selected for high or low mitotic responsiveness to PHA exhibit low or high tumor incidence, respectively, but no difference in life span, suggesting that T-cell activity is restricted to immune surveillance of neoplastic transformation. Studies on mice genetically selected for resistance or sensitivity to chemical carcinogenesis have uncovered loci that control 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 quality of life remains to be determined.
authors.affiliation: Laboratory of Immunology, AMB-PRO-TOSS, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Doria
authors.forename: G
authors.initials: G
authors.lastname: Biozzi
authors.forename: D
authors.initials: D
authors.lastname: Mouton
authors.forename: V
authors.initials: V
authors.lastname: Covelli
mesh_terms: D000375:Aging / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D007107:Immune System / Q000502:physiology*; D007111:Immunity, Cellular / Q000235:genetics; D015994:Incidence; D008136:Longevity / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology