The thymus in relation to problems of cellular growth and ageing.

Abstract

This review is an attempt to place the thymus in perspective as a special tissue, which by virtue of a high rate of cell division and ease of experimental manipulation, both in vitro and in vivo, offers unique opportunities for answering fundamental questions relating to cellular proliferation. The article begins with an account of the organ’s structure, embryonic origin and evolutionary history. Details of the role of the thymus in immunity have not been included, although current views on this topic have been summarized. Attention is also drawn to old ideas on the role of thymic products in growth and wound healing, which are worthy of further investigation. An argument is presented that the mass of the thymus is maintained as a steady state, regulated mainly by the rate of cellular death, and that organ mass is controlled largely by intrinsic non-humoral mechanisms. An account is given of work on age involution, emphasizing the possible relationship between this phenomenon and deficiencies of the immune system that occur in old age. Particular attention is paid to the role of the steroid endocrine system in age involution. Steroid hormones partly control the balance between cell division and cellular death, but their precise sites and modes of action are far from being established. Sex hormones do not determine the time of onset of age involution, and are not essential for involution to occur. Special reference has been made to the value of the thymus in studies on the ageing of mitotic cells. Recent work has stressed the possibilities of interplay between the various cell types in the tissue which is associated with a shift in the balance between cell populations with age. Morphological changes in both nucleus and cytoplasm of thymic lymphocytes indicate that ageing in these cells proceeds by an epigenetic mechanism. An important new field, with implications for experimental gerontology, is beginning to develop around experiments on thymic transplants. Transplantation work points to the importance of intrinsic processes in the control of cellular proliferation, but shows that systemic factors also play an important part in growth. Both intrinsic and extrinsic influences alter with age. The basic properties of thymic lymphocytes relating to involution change on transplantation, and this finding has important implications for cell biology in general. The final section of the review is devoted to a summary of current views on thymus and cancer. There are several similarities between proliferation of thymic lymphocytes and the growth of certain tumours, suggesting that cellular proliferation in the thymus may be worth studying as a model for work on cancerous growth.