Primary γδ 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+ αβ T cells into Th1 and Th2 subsets has become an established and important paradigm. The respective activities of these subsets appear to have profound effects on the course of infectious and autoimmune diseases. It is believed that specific programs of differentiation induce the commitment of an uncommitted Th0 precursor cell to Th1 or Th2. A component of these programs is hypothesized to be the nature of MHC-peptide antigen presentation to the αβ T cell. It has heretofore remained uncertain whether a Th1/Th2 classification likewise defines, at the clonal level, γδ T cells. Such cells do not, as a general rule, express either CD4 or CD8αβ, and they do not commonly recognize peptide-MHC. In this report, γδ 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 γδ cell clones and primary γδ cells in vivo showed a strong association of the Th2 phenotype with CD4 expression. These results are discussed with regard to the immunoregulatory role that is increasingly emerging for γδ cells.