Selective induction of growth factor production and growth factor receptor expression by different signals to a single T cell*
Stimulation of lymphokine production and the expression of receptors for growth factors can be dissociated in AK-8, a line of CD4+, I-A-restricted, conalbuminspecific mouse Tcells. When activated by antibodies specific for theTcell receptor (TcR; F23.1) or the CD3 complex (145-2C11) adsorbed to plastic culture wells, AK-8 cells produce lymphokines but are unable to proliferate. Proliferation takes place using the same stimuli upon addition of interleukin 1 (IL1). Autocrine growth induced by anti-TcR, anti-CD3 or by antigen is dependent on IL4 and not on IL2 in this cell line, as shown by the effect of antibodies against IL4 or the IL 2 receptor. Similarly to plastic-adsorbed antibodies, phorbol myristic acetate (PMA) or a combination of PMA and the calcium ionophore Ionomycin also induces secretion of growth factors without inducing proliferation, but in this case addition of IL 1 is ineffective in inducing AK-8 proliferation. When incubated with anti-TcR or anti-CD3 antibodies in soluble form these cells neither proliferate nor produce IL4 even in the presence of IL 1. However, soluble antibodies in the presence of IL 1 induce enhanced expression of IL 2 receptors, as measured both by induction of responsiveness to exogenous IL2 or flow cytometry analysis using anti-IL 2 receptor antib0dies.Thes.e results show that the pathways for the activation of growth factor receptor expression and the induction of lymphokine secretion can be differentiated in this cell line using anti-TcR or anti-CD3 reagents in different physical forms. The transmembrane signals delivered by these different forms of anti-receptor antibody may allow an understanding of these distinct requirements for T cell growth.