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.
Yamashita
N
N
Department of Microbiology and Immunology, UCLA School of Medicine 90024.
Nguyen
L
L
Fahey
J L
JL
Clement
L T
LT
D000941:Antigens / Q000276:immunology; D000943:Antigens, Differentiation; D018959:CD57 Antigens; D016827:CD8 Antigens; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008222:Lymphokines / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000941:Antigens; D000943:Antigens, Differentiation; D018959:CD57 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D008222:Lymphokines; D017493:Leukocyte Common Antigens