Natural killer (NK)-cell function and antileukemic activity of a large population of CD3(+)/CD8(+) T cells expressing NK receptors for major histocompatibility complex class I after ''three-loci'' HLA-incompatible bone marrow transplantation

We have shown that addition of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to the marrow inoculum allows engraftment of T-cell depleted, ''three loci'' HLA-incompatible marrow transplants for acute leukemia. The event-free survival of patients at high risk for relapse prompted the present investigation of the antitumor potential of this transplant. Tumor-cell lysis by natural killer (NK) cells is regulated by inhibitory receptors for specific HLA class I alleles. Here, we report the postgrafting emergence of a large, donor-type CD3(+)/CD8(+) T-cell receptor (TcR)-alpha/beta(+) cell population, barely detectable in normal subjects, that expresses 58 kD, ''p58,'' NK receptors for HLA-C locus alleles. Analysis of >900 clones revealed that 40% to 80% of these T cells exhibit NK-like function, ie, they lysed class I- targets and were functionally blocked by class I alleles on target cells. Monoclonal antibody-mediated blocking of class I recognition by these cells induced lysis of HLA-protected, autologous targets. The class I-mediated inhibitory signaling through the NK receptors also blocked TcR/CD3-triggered cytotoxicity of these cells, indicating that their antigen-specific responses may be impaired. However, the NK-like function of these cells allows them to discriminate normal cells, protected from lysis, from leukemic cells that were lysed and may be targets for a graft-versus-leukemia effect. (C) 1996 by The American Society of Hematology.