CD28 Ligation in T-Cell Activation: Evidence for Two Signal Transduction Pathways

摘要

The CD28 homodimer is thought to function as a signal transducing receptor duringactivation of T cells. Evidence is presented that the degree of aggregation of CD28 on the cell surface regulates two distinct CD28-associated signals. Binding of bivalent CD28 monoclonal antibody (MoAb) 9.3 upregulates lymphokine production by messenger RNA (mRNA) stabilization, without direct initiation of lymphokine mRNA transcription. This signal was not dependent on inositol phospholipid production or activation of a protein tyrosine kinase (PTK). In contrast, further crosslinking of CD28 on the cell surface rapidly induced formation of large amounts of inositol trisphosphate (InsP3) and increased cytoplasmic calcium concentration ((Ca2+)i), but did not stimulate PTK. CD28 crosslinking directly activated a subset of resting T cells, since CD25 (interleukin (IL)-2 receptor alpha chain) mRNA was rapidly induced in purified T cells, and proliferation, even without addition of exogenous IL-2, was sometimes observed. Keywords: Reprints, Medical research, CD28, T-Lymphocyte, Signal transduction, Phosphilipase-C, Tryosine phosphorylation, Ligation, T-Cell activation, PTK, Phorbol-12-myristate-13-acetate (PMA). (jg)