Human double-negative (CD4-CD8-) T cells bearing αβ T cell receptor possess both helper and cytotoxic activities

Expression of CD4 or CD8 on the cell surface is an important guide for discriminating the immunological functions of T cells. However, a minor T cell subset, which lacks both CD4 and CD8 molecules but bears the usual form of T cell receptor (TCR) alpha beta (CD4-CD8-TCR alpha beta+ T cells), has recently been found not only in mice but also in humans, and its role in immune response is now of considerable interest. In order to clarify the characteristics of this newly defined T cell subpopulation, we established five IL-2-dependent CD4-CD8-TCR alpha beta+ T cell clones from the peripheral blood of a healthy individual, and examined their various biological functions. It was found that all clones not only helped B cells in immunoglobulin production, but also exerted major histocompatibility complex-unrestricted cytotoxicity. Although their CD3/TCR complexes were functionally competent, the cytotoxicity seemed to be mediated via unknown molecules other than the CD3/TCR complex, as evidenced by the failure of CD3 MoAb to inhibit the cytotoxic activity. Our present findings showed that CD4-CD8-TCR alpha beta+ T cells possess potential bifunction, i.e. helper and cytotoxic activities. Their roles in the pathogenesis of immunodeficiency are discussed.