Effect of thymulin on intracellular cyclic nucleotides and prostaglandins E2 in peanut agglutinin-fractionated thymocytes

Abstract

Prostaglandin E2 (PGE2) and other selected agents which elevate intracellular cyclic AMP (cAMP) levels have been demonstrated to induce the appearance of surface markers in immature T lymphocytes. Thymic hormones, which are the natural inducers of these markers, have long been hypothesized to act through the increase of cAMP levels. We have approached this area of investigation by studying the effects of thymulin (a serum thymus-derived factor, coupled with Zinc) on intracellular cAMP and cyclic GMP (cGMP) levels (expressed as cAMP/cGMP ratio) and on the release of PGE2 in different thymocyte subpopulations. Thymocytes were fractionated by the peanut agglutinin (PNA) technique into cortical immature PNA+ and medullary mature PNA- thymocytes. The data presented in this report show that thymulin is able to increase the cAMP/cGMP ratio in PNA+ and in unfractionated thymocytes, depending on its concentration, but not in PNA- thymic cells. Conversely, it is able to increase the release of PGE2 by PNA- thymocytes but not by PNA+ and unfractionated thymic lymphocytes. These results are consistent with the hypothesis that thymulin could act through different mechanisms depending on the differentiation stage of its target cells. In fact, it could be suggested that immature T cells could be activated by thymulin thereby increasing the cAMP/cGMP ratio, whereas more mature T cells would be further differentiated by thymulin through enhanced release of PGE2.