IFN-gamma R expression is subject to contrasting modulation on human T cells. IFN-gamma R constitutive expression is low on three human malignant T cells (ST4, PF382, and Jurkat) growing in medium supplemented with serum. The addition of IFN-gamma down-modulates IFN-gamma R expression and increases both proliferation and MHC class I Ag expression. By contrast, when malignant T cells are cultured in medium without serum, IFN-gamma R expression dramatically increases and the cells undergo a slow apoptotic death. The addition of IFN-gamma enhances apoptosis and inhibits cell rescue in serum-supplemented medium. This opposite ability of IFN-gamma to stimulate malignant T cell proliferation or death correlates with the intensity of IFN-gamma R cell expression, high expression being a marker for cell apoptosis. IFN-gamma R up-modulation also occurs on malignant T cells undergoing apoptosis after treatment with dexamethasone, on irradiated normal CD3+ PBL, and on cultured normal CD3+ thymocytes. Moreover, the ability of IFN-gamma to augment apoptosis of highly IFN-gamma R-positive thymocytes suggests that its role in promoting T cell apoptosis is also important in physiologic conditions.

Summary:The measurement of precursor frequencies of donor anti-recipient cytotoxic T lymphocytes (CTL-p) has been shown to predict the incidence and the severity of acute graft-versus-host disease (aGVHD) in unrelated donor bone marrow transplantation (BMT). In HLAidentical sibling BMT, where aGVHD is most likely caused by minor histocompatibility antigen mismatches, this assay did not appear to be sensitive enough to provide similar predictive information. In this study, the CTL-p frequencies and the incidence and severity of aGVHD in 51 onco-hematological patients transplanted from HLA-identical siblings were compared. Sibling donors were selected on the basis of HLA identity using serological typing for HLA-A, B, C antigens, whereas HLA-DRB was tested by molecular analysis. Sibling identity was also confirmed by DNA heteroduplex analyses.

In recent years, the anti-leukemic potential of Natural Killer (NK) cells and their role in hematologic malignancies and in Hematopoietic Stem Cell Transplants (HSCT) has attracted greater interest and a recent study by Cooley S. et al. showed a better clinical outcome when patients with Acute Myeloid Leukemia received a transplant from unrelated Group B KIR haplotypes donors. As a consequence of these results, an algorithm called "KIR B-content score" was formulated. The aim of our research is a retrospective analysis of HSC unrelated transplants performed in our center to analyze the effect of the donor KIR B status on the clinical-outcome. Our results showed a better overall survival-rate in the AML recipients, HLA mismatched with the donor, when the donor KIR B content status is Best/Better (37% vs 18% at three years P=0,028). Moreover, we observed that AML recipients, whose Donors KIR B status was Best/Better, had more incidence of aGvHD grade I and II than patients whose Donors KIR B status was Neutral (70% vs 26%) and also a lower rate of relapse (36% vs 58%) and a better Disease Free Survival-rate (58% vs 38% at three years P=0,1) because of a better GvL effect.

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