Phorbol esters and CAMP differentially regulate the expression of CD4 and CD8 in human thymocytes

The present study shows that stimulation of human thymocytes by phorbol esters or cAMP result in a differential regulation of CD4 and CD8 expression, both at the mRNA and cell surface glycoprotein level.The differential regulation of CD4 and CD8 gene expression suggests that the selective activation of protein kinase C (PKC) and cAMP-dependent protein kinases (PKA) may be required for the selection of single positive CD4+CD8- and CD4-CD8+ cells during Intrathymic differentiationT-lymphocytes expressing the α:β T-cell antigen receptor (TCR) consist of two major subsets: T cells expressing the CD4 surface glycoprotein, which are restricted by the major hystocompatibility complex (MHC) class II proteins, and CD8+ T cells, which interact with antigen presented by MHC class I proteins [1]. CD4 and CD8 molecules bind to monomorphic regions on class II and class I MHC proteins respectively, thereby increasing the avidity in the interaction of the TCR with antigen presenting cells [2]. An intriguing question concerns to the mechanism by which selection and tolerance to self-components is mediated in developing lymphocytes. This is particularly relevant to T Lymphocytes because of their ability to recognize antigen only if this is associated with the class I or the class II MHC molecules [3], and also because of the unique selection process which operates within the thymus during T cell development. Early during T-cell development in the thymic cortex, thymocytes bear both of the T cell surface glycoproteins CD4 and CD8 and express the α and β heterodimer of the TCR [4]. Compelling data have demonstrated that CD4 and CD8 molecules participate in the selection of MHC class I or class II restricted T cells in the thymus. It is known that during clonal selection in the thymus, immature CD4, CD8 double positive cells develop into single positive CD4 or CD8 cells according to the relative affinity of their TCR to class II or class I molecules respectively [5,6]. These immature T-