Human T-cell activation: comparative studies on the role of different phorbol esters.

We confirm here previous studies that have shown synergy between anti-CD3 and phorbol esters in the induction of T-cell proliferation. However, for this study we have used tonsillar rather than peripheral blood T cells, and have compared the role of different phorbol esters rather than different anti-CD3 antibodies in the activation process. Three phorbol esters (phorbol myristate acetate, -dibenzoate and -didecanoate) showed a synergistic relationship. However, the concentration of the dibenzoate and the didecanoate forms required was higher than the concentration of myristate acetate. A second group of phorbol esters (alpha-phorbol didecanoate, a beta phorbol with no side chain, and a monomyristate) did not activate T cells. This difference in activation efficiency between the phorbol derivatives correlates with the pattern of neutrophil activation that has been described previously using the same compounds. In contrast to both the neutrophil and the proliferation studies, if the T cells were preincubated with the different phorbol esters and then subsequently cultured with anti-CD3, the pattern of response was different. Only phorbol myristate acetate induced a proliferative response; all the other compounds were inactive. Taken in conjunction with the known structural differences between the different phorbol derivatives, these results suggest that the relative lipophilic properties of the different molecules which activate T cells may be an important determinant in the induction of a response. Thus changes in the relative lipophilic properties of an antigen could be one way to alter its relative immunogenicity.