DIFFERENTIAL SENSITIVITY OF CD4+ AND CD8+ LYMPHOCYTE-T TO PHORBOL-MYRISTATE ACETATE UPON ANTI-CD3 STIMULATION - EVIDENCE FOR A DISTINCT SIGNALING PATHWAY

The effects of suboptimal concentrations of Phorbol Myristate Acetate (PMA) in combination with submitogenic concentrations of OKT3 antibody on CD4+ and CD8+ cell activation were investigated. Upon stimulation with OKT3 (25 pg/ml) and PMA (0.25 - 0.75 ng/ml), the majority of CD4+ cells entered the cell cycle whereas most of CD8+ cells remained in G0/G1 phase. Under the same conditions of OKT3 stimulations, both CD4+ and CD8+ cells failed to produce IL2 in the absence of PMA. In the presence of PMA (0,25 ng/ml), CD4+ produced measurable amounts of IL2 (0,5 - 2,3 U/ml) whereas IL2 production by CD8+ cells remained below the detection limit. Expression of TAC antigen (CD25) was found to parallel IL2 production and cell proliferation in both subsets whereas changes in [Ca2+] mobilization following OKT3 stimulation were similar in both subsets. Interestingly, the elevation of intracellular cyclic adenosine 3':5' monophosphate (cAMP) was not equally distributed between CD4+ and CD8+ subpopulations. Furthermore, the kinetics of protein kinase (PKC) translocation was markedly prolonged in membranes of CD4+ cells compared with CD8+ cells suggesting a differential involvement that may operate under distinct regulatory signaling mechanisms.