期刊
BONE MARROW TRANSPLANTATION
卷 27, 期 10, 页码 1087-1093出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bmt.1703043
关键词
stem cell transplantation; graft-versus-leukemia; gamma delta T cell receptor; cytotoxic T lymphocytes; killer cell-inhibitory receptor; CD158b
Cytotoxic T lymphocytes (CTL) are thought to play an important role in the graft-versus-leukemia (GVL) response. Unfortunately, GVL reactivity is often associated with life-threatening graft-versus-host disease (GVHD), Characterization of CTL that selectively attack leukemic cells but not normal cells may lead to the development of adjuvant immunotherapy that separates GVL from GVHD, Here, we describe TCP gamma delta (V beta9/V delta1) CTL, isolated from the peripheral blood of an AML patient after stem cell transplantation (SCT), that very efficiently lysed freshly isolated acute myeloid leukemia (AML) cells and AML cell lines. Interestingly, HLA-matched non-malignant hematopoietic cells were not killed. We revealed that the killer cell-inhibitory receptor (KIR) p58.2 (CD158b) specific for group 2 HLA-C molecules negatively regulates the cytotoxic effector function displayed by these TCR gamma delta CTL, First, an antibody against HLA-C enhances lysis of nonmalignant cells. Secondly, stable transfection of HLA-Cw*0304 into the class I-negative cell line 721.221 inhibited lysis, Finally, engagement of p58.2 by antibodies immobilized on Fc gammaR-expressing murine P815 cells inhibits CD3- and TCR gamma delta -directed lysis, Compared to non-malignant hematopoietic cells, AML cells express much lower levels of MHC class I molecules making them susceptible to lysis by p58.2(+) TCR gamma delta CTL, Such KIR-regulated CTL reactivity may have a role in the GVL response without affecting normal tissues of the host and leading to GVHD.
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