Mitogen-induced human T cell proliferation is associated with increased expression of selected PKC genes

Abstract

The induction of T cell proliferation and differentiation into mature effector cells is dependent on two principal exogenous signals that are provided by the antigen or mitogen and IL2. The enzyme protein kinase C (PKC) has a major role in the antigen-receptor signalling pathway in T cells, but appears not to be involved in signalling via the IL2-receptor (IL2-R). Since both pathways trigger a series of sequentially coordinated transcriptional events in which numerous genes are activated, we tested whether a T cell mitogen acting via the TCR/CD3 complex, and IL2, affect the expression of the conventional, Ca 2+-dependent, PKC genes (α, β and γ) in T cells. Stimulation of human peripheral blood lymphocytes or an enriched population of human T cells with phytohemagglutinin resulted in augmented mRNA levels of PKCα and PKCβ, but not PKCγ-gene. The response peaked at 24–48 hr when a 3–5-fold increase was observed. Stimulation of IL2-Rα-expressing T cells with human recombinant IL2 induced cell proliferation and transcription of the IL2-Rα gene (> 100-fold), but did not change mRNA levels of PKCa or PKCβ genes. The results suggest that stimulation of human T cells with mitogens acting via the TCR/CD3 complex, that involve activation of PKC, is accompanied also by a late activation of selected PKC genes. By contrast, agonists such as IL2, that operate via a different signalling pathway, do not modify the expression of any of the known conventional PKC genes.