Thymic atrophy in the mouse is a soluble problem of the thymic environment

Age related deterioration in the function of the immune system has been rec ognised in many species. The clinical presentations of such immune dysfunct ion are an age-related increased susceptibility to certain infections, and an increased incidence of autoimmune disease and certain cancers. Laborator y investigations reveal a reduced ability of the cells from older individua ls, compared with younger individuals, to perform in functional in vitro as says. These manifestations are thought to be causally linked to an age asso ciated involution of the thymus, which precedes the onset of immune dysfunc tion. Hypotheses to account for the age-related changes in the thymus inclu de: (i) an age related decline in the supply of T cell progenitors from the bone marrow (ii) an intrinsic defect in the marrow progenitors, or (iii) p roblems with rearrangement of the TCR beta chain because of a defect in the environment provided by the thymus. We have analysed these possible option s in normal mice and also in mice carrying a transgenic T cell receptor. Th e results from these studies reveal no age related decline either in the nu mber of function of T cell progenitors in the thymus, but changes in the th ymic environment in terms of the cytokines produced. We have shown that spe cific cytokine replacement therapy leads to an increase in thymopoiesis in old animals. (C) 2000 Elsevier Science Ltd. All rights reserved.