Expression of GTP-binding proteins and prostaglandin E₂ receptors during human T cell activation

GTP-binding proteins (G-proteins) are a family of closely related, yet structurally distinct signal transducing proteins. In this study the presence and relative abundance of several G-proteins and of their corresponding mRNAs were measured in resting and activated human T lymphocytes. We found that T lymphocytes contain RNA coding for G_s, G_i2, and G_i3. No G_i1- and G_o specific RNA could be detected. Membrane fractions of resting and activated lymphocytes were studied in immunoblot experiments. Again, G_s, G_i2, and G_i3, but not G_i1 and G_o, were detected. Upon mitogenic activation, a relative increase in mRNA for G_s and G_i3, but not for G_i2 could be demonstrated in Northern blot experiments. Immunoblotting indicated an increase in G_s and G_i3 density in membrane fractions of T cells as well. Paralleling the increase in G_s, we found that activated T cells produce five to seven times more CAMP per cell in response to prostaglandin E₂ (PGE₂) than resting lymphocytes. Finally, PGE₂ binding studies showed that the number of receptors for this hormone increased from 435 ± 322 to 1035 ± 357 per cell following in vitro stimulation. We propose that in vitro T cell activation is paralleled by an increase in sensitivity to PGE₂-induced cAMP generation. This sensitization is accompanied by both an increase in cell surface PGE₂ receptor numbers as well as by increased expression of the signal transducing protein G_s and may physiologically be important for limiting an immune response.