Phenotypic properties and cytotoxic functions of human CD8+ cells expressing the CD57 antigen.

The CD8+CD57+ granular lymphocyte subset is significantly expanded in a number of clinical disorders. Because several studies have suggested that CD8+CD57+ cells might be in vivo primed, antigen-specific cytotoxic T lymphocytes, we have analyzed the phenotypic and functional properties of CD8+CD57+ cells. Using three-color flow cytometry, virtually all freshly isolated CD3+CD8+CD57+ cells were found to have phenotypic properties characteristic of 'naive' T lymphocytes; these cells coexpressed the CD45RA antigen, lacked expression of the CD45RO antigen, and expressed reduced levels of CD58 adhesion molecules. When purified CD45RA+ T cells were stimulated with alloantigens, approximately 50% of CD8+CD57- cells lost CD45RA antigen expression. In contrast, CD8+CD57+ cells (which were > 90% CD3+) remained CD45RA+. Although CD8+CD57+ cells could mediate lectin-dependent cytotoxicity, both before and after the mixed lymphocyte reaction cultures, CD8+CD57+ cells had no antigen-specific cytotoxic activity against allogeneic target cells; only the subset of CD8+CD57- cells which converted to the CD45RA- phenotype had specific cytotoxic activity. Interestingly, although CD8+CD57+ cells did not lyse allogeneic cells, 50-90% of these cells acquired HLA-DR antigen expression during the mixed lymphocyte reaction. This did not appear to be a passive effect produced solely by lymphokines, because soluble factors released by alloactivated T cells induced only modest HLA-DR expression on purified CD8+CD57+ cells. Thus, whereas CD8+CD57+ cells may become activated when in the milieu of an immunologically specific response, our data suggest that these cells do not develop into or appear to represent antigen-specific cytotoxic T cells.