Thymic hormones.

Abstract

The thymus produces several polypeptides, which induce lymphocyte differentiation in vitro and in vivo. Several of these polypeptides have been chemically characterized, and three of them have been sequenced and synthesised (alpha 1 thymosin, thymopoietin and the serum thymic factor). Thymic hormones do not act identically on all T-cell subsets: they alter preferentially post-thymic precursor cells, and among mature T cells cytotoxic cells and suppressor cells. Their mode of action at the cellular level involves binding to specific cellular receptors and interaction with adenyl cyclase. Preliminary clinical trials with crude extracts have provided promising results in immunodeficient and cancer patients. The differentiation of T cells from stem cells has been the matter of considerable investigation over the last two decades, since it has been realized that the thymus and its products, the thymus-derived cells (T cells) play a central role in the generation of effector cells in cell-mediated immunity and in the regulation of the various categories of immune responses. That the thymus could act by the intermediate of humoral substances was precociously suggested by MILLER and OSOBA before the observation that thymuses grafted within a cell-impermeable Millipore diffusion chamber restored the immunocompetence of neonatally thymectomized (Tx) mice (1). However, although this experiment was ultimately confirmed by using chambers with well-controlled impermeability (2), MILLER did not pursue the idea of the humoral function of the thymus. Probably, the striking results obtained by DAVIES (3) and other workers, indicating direct migration of functional T cells from the thymus and the poor results initially obtained in trying to reconstitute the immune system of neonatally Tx mice by cell-free thymic extracts contributed to this disappointment. A new impetus was given to the subject in the early 70's when in vitro tests of lymphocyte function became available and when purified extracts of the thymus proved capable of restoring antigen-specific and non-specific immunocompetence of Tx mice. More recently, completely defined synthetic thymic hormones have been obtained. The question is no longer to decide whether thymic hormones exist, but rather to elucidate their biological significance and potential clinical applications. The multiplicity of available factors has created some confusion. It will be the aim of these few pages to review critically the various factors reported in the literature, giving particular emphasis to their pharmacology and their potential use in the modulation of immune responses.