PRIMARY GAMMA-DELTA CELL CLONES CAN BE DEFINED PHENOTYPICALLY AND FUNCTIONALLY AS TH1 TH2 CELLS AND ILLUSTRATE THE ASSOCIATION OF CD4 WITH TH2 DIFFERENTIATION/

The division of CD4(+) alpha beta T cells into Th1 and Th2 subsets has become an established and important paradigm. The respective activiti es of these subsets appear to have profound effects on the course of i nfectious and autoimmune diseases. It is believed that specific progra ms of differentiation induce the commitment of an uncommitted Th0 prec ursor cell to Th1 or Th2, A component of these programs is hypothesize d to be the nature of MHC-peptide antigen presentation to the alpha be ta T cell. It has heretofore remained uncertain whether a Th1/Th2 clas sification likewise defines, at the clonal level, gamma delta T cells, Such cells do not, as a general rule, express either CD4 or CD8 alpha beta, and they do not commonly recognize peptide-MHC. In this report, gamma delta cell clones are described that conform strikingly to the Th1/Th2 classification, both by cytokine expression and by functional activities of the clones in vitro and in vivo. Provocatively, both the gamma delta cell clones and primary gamma delta cells in vivo showed a strong association of the Th2 phenotype with CD4 expression. These r esults are discussed with regard to the immunoregulatory role that is increasingly emerging for gamma delta cells.