Differential Sensitivity of CD4 + and CD8 + T Lymphocytes to Phorbol Myristate Acetate upon Anti-CD3 Stimulation: Evidence for a Distinct Signaling Pathway

Abstract

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.