Mitogen-induced human T cell proliferation is associated with increased expression of selected PKC genes.
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 (alpha, beta and gamma) 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 PKC alpha and PKC beta, but not PKC gamma-gene. The response peaked at 24-48 hr when a 3-5-fold increase was observed. Stimulation of IL2-R alpha-expressing T cells with human recombinant IL2 induced cell proliferation and transcription of the IL2-R alpha gene (greater than 100-fold), but did not change mRNA levels of PKC alpha or PKC beta 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.
Isakov
N
N
Department of Microbiology and Immunology, Ben Gurion University of the Negev, Beer Sheva, Israel.
Mally
M I
MI
Altman
A
A
D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics; D008213:Lymphocyte Activation; D009955:Ornithine Decarboxylase / Q000235:genetics; D010835:Phytohemagglutinins / Q000008:administration & dosage; D011493:Protein Kinase C / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors
D007376:Interleukin-2; D007527:Isoenzymes; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase