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 recognised in many species. The clinical presentations of such immune dysfunction are an age-related increased susceptibility to certain infections, and an increased incidence of autoimmune disease and certain cancers. Laboratory investigations reveal a reduced ability of the cells from older individuals, compared with younger individuals, to perform in functional in vitro assays. These manifestations are thought to be causally linked to an age associated involution of the thymus, which precedes the onset of immune dysfunction. Hypotheses to account for the age-related changes in the thymus include: (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) problems with rearrangement of the TCR beta chain because of a defect in the environment provided by the thymus. We have analysed these possible options in normal mice and also in mice carrying a transgenic T cell receptor. The results from these studies reveal no age related decline either in the number of function of T cell progenitors in the thymus, but changes in the thymic environment in terms of the cytokines produced. We have shown that specific cytokine replacement therapy leads to an increase in thymopoiesis in old animals.
Aspinall
R
R
Department of Immunology, ICSM at Chelsea and Westminster Hospital, 369 Fulham Road, London, UK. r.aspinall@ic.ac.uk
Andrew
D
D
D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D001284:Atrophy; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D015851:Interleukin-7 / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*
D015851:Interleukin-7; D016693:Receptors, Antigen, T-Cell, alpha-beta