Utility of adenovirus-mediated Fas ligand and bcl-2 gene transfer to modulate rat liver allograft survival

BACKGROUND: Expression of Fas ligand (FasL) on the graft by gene transduction is expected to introduce apoptosis to lymphocytes to protect rejection, but the FasL-expressing graft cells may also induce apoptosis as the graft usually expresses Fas antigens. In this study, a strong antiapoptotic gene, bcl-2, was cotransfected with the FasL gene in rat liver graft to protect against Fas- mediated cell death and to prolong recipient survival. METHODS: Orthotopic liver transplantation was done in a strain combination of DA to LEW rats. After donor vascular isolation, adenovirus-mediated FasL and bcl-2 genes were cotransfected in the liver graft. RESULTS: Intragraft expression of FasL mRNA was constitutively expressed after adenovirus-mediated transduction, although expression of FasL increased mildly in control grafts. Bcl-2 mRNA was highly expressed at 2 days after reperfusion. In contrast, lower expression of bcl-2 was observed in the control group. The average survival of the gene transferred allografts increased from (9.8+1.3) days to (18.5+8.7) days compared with the control group. CONCLUSION: Our results indicate that rat liver allografts can be protected against host immune responses by adenovirus-mediated FasL and bcl-2 transfection, and that bcl-2 expression prevents the graft from Fas-mediated apoptosis.

EXPRESSION OF MATRIX METALLOPROTEINASE-7 AND FAS LIGAND: THEIR APOPTOSIS-INDUCING EFFECT ON GASTRIC CANCER CELLS

Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and embedded tissues of primary gastric cancer and adjacent non-tumor mucosa from 113 cases were evaluated for MMP-7, FasL and Capase-3 expression by streptavidin-peroxidase (S-P) immunohistochemistry. The expression of the first two proteins in cancer cells of primary foci was compared with clinicopathological parameters of tumors. We also observed the correlation of MMP-7 and FasL expression with Caspase-3 expression in cancer cells of primary foci. Results: MMP-7 positive immunostaining was less frequently detected in adjacent epithelial cells than in cancer cells of primary foci of gastric cancer (P<0.05, 29.2% vs 69.0%), and so was FasL (P<0.05, 34.5% vs 54.0%). MMP-7 expression was associated with tumor size, Borrmann抯 classification, invasive depth, metastasis and TNM staging (P<0.05), but not with growth pattern, Lauren抯 classification, or histological classification (P>0.05). FasL expression was correlated with tumor size, invasive depth, metastasis, Lauren抯 classification, histological classification (P<0.05), while not with Borrmann抯 classification, TNM staging or growth pattern (P>0.05). Cancer cells of primary foci expressed less Caspase-3 than their adjacent epithelial cells (P<0.05, 32.7% vs 50.4%). There was an obvious correlation between FasL, MMP-7 and Caspase-3 expression in cancer cells of primary foci (P<0.05). Co-expression of MMP-7 and FasL paralleled with Caspase-3 expression in cancer cells of primary foci (P<0.05). Conclusion: MMP-7 and FasL expression was up-regulated in gastric carcinogenesis and was principally involved in progression of gastric cancer. FasL expression could reflect the differentiation of gastric cancer cells and underlie the molecular mechanisms of different pathways of gastric tumorigenesis. Co-expression of MMP-7 and FasL could have apoptosis-inducing effect on gastric cancer cells.

Association between Up-regulation of Fas Ligand Expression and Apoptosis of Tumor-infiltrating Lymphocytes in Human Breast Cancer

In order to study the significance of FasL expression in immune escape of breast cancer, FasL protein expression and the number of tumor-infiltrating lymphocytes （TILs） in 40 specimens of breast cancer were detected by immunohistochemitry. The expression of FasL mRNA was measured by in situ hybridization in the consecutive tissue slices of 40 breast cancers respectively. By using terminal deoxynucleotidyl transferase-mediaed dUTP nick end labeling （TUNEL）, apoptotic cells were detected in 40 specimens of breast cancer. The expression of FasL was detected in all 40 specimens to varying degrees. In the consecutive tissue slices, the location of expression of FasL protein corresponded with that of FasL mRNA. In those with FasL extensive expression, the number of TILs was less （P〈0.05）, the apoptotic index （AI） of TILs was higher and the AI of tumor cells was lower （P〈0.01） than those with FasL weak expression respectively. The AI of TILs was correlated with that of tumor cells （r=-0.629, P〈0.01）. In conclusion, breast cancer cells can induce the apoptosis of TILs through the expression of FasL, which can counterattack the immune system. This may be a mechanism of immune evasion in breast cancer.

Study on the Expression of Fas Ligand on the Surfaces of Human Cytotrophoblasts in Normal Pregnancy

To further study the mechanism of maternal-fetal immune tolerance, the expression of Fas ligand (FasL) on the surfaces of human cytotrophoblasts in normal pregnancy was detected by using immunohistochemical method. High precise color-image measure system for immuno-histo- chemistry was used to quantitatively analyze the expression of FasL. The results showed that FasL were expressed on the surfaces of placental cytotrophoblasts throughout normal pregnancy. The variance among the first, second and term pregnant stages was also detected. It was suggested that the expression of FasL on the surfaces of placental cytotrophoblasts might play an important role both in the maintenance of pregnancy and in the normal development of fetus. The maternal speific T cell apoptosis induced by Fas/FasL is one of the significant mechanisms of maternal-fetal immune tolerance.

Effects of Ureaplasma Urealyticum on Fas Ligand Expression in Rat Sertoli Cell

To investigate the effect of ureaplasma urealyticum (UU) on the expression of Fas ligand (FasL) on rat Sertoli cell Materials & Method Isolated rat Sertoli cells were infected by living UU, UU super- natants, inactivated UU, then Fluorescence Activated Cell Sorter and observed fluores- cence microscopy were used to assay for the FasL expression on the surface of Sertoli cells. Results UU infection could increase the expression of FasL in Sertoli cell. Conclusion The functional expression of FasL is related to the immune privilege and can give the immune regulation on the testis.

EXPRESSION OF Fas LIGAND IN HUMAN COLON CANCER CELL LINES

Objective: To investigate the expression of Fas ligand in human colon carcinoma cell lines. Methods: A total of six human colon cancer cell lines were examined for the expression of Fas ligand mRNA and cell surface protein by using RT-PCR and flow cytometry respectively. Results: The results showed that Fas ligand mRNA was expressed in all of the six cancer cell lines and Fas ligand cell surface protein was expressed in part of them. Conclusion: These data suggest that Fas ligand was expressed, at least in part, in human colon cancer cell lines and might facilitate to escape from immune surveillance of the host.

Apoptosis of Leukemia Cells Induced by CD34^+ Cells Transferred Exogenous Fas Ligand

To assess the value of CD34 + cells transferred exogenous Fas ligand (FasL) in inducing apoptosis of human leukemic cells, the CD34 + cells transfected with F asL or without, pretreated with mitomycin C, was mixed with leukemic cell line U937 cells in presence or absence of daunorubicin (DNR) or cytosine arabinoside (Ara C). After l8 h, apoptosis of cells was detected by FCM and TUNEL. Induced for l8 h by CD34 + cells transfected with FasL or without, the ratio of apoptos is of U937 cells was (5.0±1.3) %, (10.8±0.6) % ( P < 0.01), respectively. Induced by FasL +CD34 ++DNR, FasL +CD34 ++Ara C, the ratio was (13.4±1.0) % ( P < 0.05), (17.9±1.3)% ( P <0.01), respectively. The result demonstrated that CD34 + cells transfected with exogenous FasL could induce apoptosis of human leukemic cells and showed a cytotoxic synergistic effect when used in combination with chemotherapeutic drugs, suggesting that it was possible to develop a new method in treatment of leukemia.

The Serum Levels of Soluble Fas Ligand and Soluble Fas Receptor in Patients with chronic congestive heart failure

Objectives To investi gate the association of soluble Fas ligand( sFasL) and soluble Fas receptor( sFas) with human chronic con gestive heart failure( CHF) . Methods The serum level of sFasL and sFas in 33 patients with CHF (13 in cardiac function class Ⅱ, 17 in class Ⅲ, 3 in class Ⅳ, NYHA) was assessed with enzyme - linked immunosorbent assay, and was compared with that of 18 age - , blood pressure - matched patients with car diac function class Ⅰ (NYHA). Results There was no difference in the level of sFasL between the two groups [CHF group: 231. 50 + / - 84. 50 (cardiac function class Ⅱ216. 50 + / - 96. 00 , class Ⅲ 226. 80 + / - 85. 70, class Ⅳ 244. 00 + / - 73. 00) vs. cardiac function class I group: 217. 50 + /-89. 00 pg/mL, P>0. 05]. However, the level of sFas was significantly higher in the patients with CHF than those of cardiac function class I group [CHF group: 1353. 30 +/-507. 71 (cardiac function class Ⅱ 1154. 85 + /-371. 20 , class Ⅲ1412.88 + /-493. 62, classⅣ1875. 67 + / - 806. 10) vs. cardiac function class I group: 983. 11+/ -461. 26 pg/mL, P<0. 05 ] . Conclusions sFasL was not associated with human CHF. However, the elevation of serum level of sFas was proportion to the severity of human CHF. sFas may play an important role in the patho- genesis of human CHF.

Fas ligand在宫颈癌形成中的作用及机制研究进展

FasL(Fas ligand)是一种II型膜蛋白,属于肿瘤坏死因子家族,在体内参与诱导细胞凋亡,发挥一定生理作用。同时,FasL在许多肿瘤组织中高表达,在宫颈癌的发生发展、转移及侵袭中发挥重要作用,其具体作用机制涉及多条信号通路,包括参与肿瘤细胞的被动逃逸与主动攻击、维持机体炎症状态以及发出非凋亡信号促进肿瘤发生等。FasL高表达会导致不良的肿瘤预后,降低患者生存率。由于FasL可参与肿瘤细胞免疫逃逸,因此,针对FasL的靶向治疗可能为肿瘤基因治疗或免疫治疗提供一个新的方向。该文对FasL在宫颈癌发生发展中的作用机制及其在治疗方面的应用加以综述,从而为探索新的宫颈癌治疗靶点提供科学依据。

Inducing apoptosis and upregulation of Bax and Fas ligand expression by allicin in hepatocellular carcinoma in Balb/c nude mice

Many health benefits have been ascribed to allicin, including vasorelaxant activities. However, the molecular mechanisms underlying these effects remain unknown. To apply allicin in clinical anti-HCC treatment, different doses of allicin and Adriamycin （ADM） were led into transplanted tumor model established by injecting HCC BEL7402 cells into subcutaneous tissue of nude mice. Treatment with allicin and ADM resulted in tumor regression with inducing of Bax and Fas ligand （FasL） mRNA.

Distinct Overexpression of Fas Ligand on T Lymphocytes in Aplastic Anemia

Increased expression of Fas by hematopoietic progenitors in aplastic anemia(AA)suggests that Fas/Fas ligand (FasL)system plays a key role in the formation of severe pancytopenia.To further confirm the above hypo- thesis,T cells from 8 patients with AA were systematically studied for their FasL's distribution pattern, releasing manner and proapoptotic activity,compared with normal resting T cells and artificially activated T cell blasts.The results demonstrated that AA T cells abnormally expressed low levels of membrane-bound FasL and contained high levels of intracellular FasL which could be triggered to release by high-dose phyto- hemagglutinin(PHA)pulse-stimulation.The supernatants from the PHA-stimulated AA T cells had apparent cytotoxicity against FasL-sensitive Jurkat cells,which could be significantly inhibited by monocional antibody against FasL in a dose-dependent manner,or nearly completely abrogated by ultracentrifugation.The above phenomena also appeared on artificially activated T cell blasts,but this was not the case on normal resting T cells.These results indicate that AA T cell is a type of“preactivated”T lymphocyte,characterized by over- expression of FasL,especially intracellular FasL which can be stimulated to release in bioavtive exosomes- bound form.Taken together,our data provide further and direct evidence for the hypothesis that T cells might mediate the destruction of hematopietic progenitor in AA through Fas/FasL system.Cellular & Molecular Immunology.2004;1(2):142-147.

Oral administration of insulin to female nonobese diabetic mice inhibited diabetes and induced Fas ligand expression on islets of Langerhans

To detect oral administration of recombinant human insulin to nonobese diabetic (NOD) mice for preventing them from diabetes and insulitis and to detect the effects of oral administration of insulin on Fas and Fas ligand expression on islet of Langerhans Methods Sixty four female NOD mice were divided into two groups One group (34) was orally administered recombination human insulin 1?mg in 500?μl PBS and the other (30) 500?μl PBS only at age of 5 weeks old, twice a week for the first week, then weekly until 30 weeks of age Results Oral administration of insulin to female NOD mice can significantly suppress diabetes and insulitis The insulitis was less severe in the group fed with insulin than that in the control group (score of insulitis: 1 25±0 45 vs 3 0±0 76 at 16 weeks of age, P <0 01) We examined Fas ligand and Fas expression on islets of Langerhans in both groups of NOD mice by using immunohistochemical techniques We find that Fas only expressed on islets when the mice suffered the diabetes, whereas Fas ligand expressed on islets of the mice fed with insulin at 16 and 20 week of ages We did not find Fas ligand positive staining on the islet feeding with PBS Conclusion We speculated that oral insulin may induce Fas ligand expression on the islets and plays a role in protecting the pancreatic β cell from autoimmune destruction These results show that oral insulin affected autoimmune diabetes and insulitis in NOD mice The immune mechanism of oral tolerance is closely related to the change of Fas ligand and Fas system

Clinical significance of Fas and FasL protein expression in gastric carcinoma and local lymph node tissues

AIM:To investigate the relation of Fas and Fas ligand (FasL) protein expression with carcinogenesis and metastasis of gastric carcinoma.METHODS: Immunohistochemistry was used to detect Fas and FasL protein expression in 64 gastric carcinoma tissue samples and 20 normal gastric tissue samples. Relation between FasL and Fas expression, age and gender of gastric cancer patients, and pathological subtype and lymph node metastasis of gastric cancer was analyzed.RESULTS: The Fas expression level was significantly higher in normal gastric tissue samples than in gastric carcinoma tissue samples (85.0% vs 25.0%, P<0.001), while the FasL expression level was signif icantly lower in normal gastric tissue samples than in gastric carcinoma tissue samples (30.0% vs 81.3%, P<0.001). The Fas expression level was significantly higher in invasive lymph nodes than in non-invasive lymph nodes (82.9% vs 56.5%, P<0.003) and in well-differentiated gastric carcinoma tissue samples than in poorly-differentiated gastric carcinoma tissue samples (50.0% vs 18.0%, P=0.015). The FasL expression level was significantly lower in well-differentiated gastric carcinoma tissue samples than in poorly-differentiated gastric carcinoma tissue samples (42.9% vs 84.0%, P=0.021). The Fas and FasL expression levels (25.0% and 81.3%) were signif icantly different in gastric carcinoma tissue samples (P<0.001), but had a non-linear correlation (P=0.575).CONCLUSION: Abnormal Fas and FasL expressions in gastric carcinoma and lymph node tissues are involved in carcinogenesis and metastasis of gastric cancer.

FasL Expression in Colorectal Carcinoma and Its Significance in Immune Escape of Cancer

To study the significance of FasL expression in immune escape of colorectal carcinoma, FasL protein expression and the number of tumor infiltrating lymphocytes （TILs） in 80 specimens of colorectal carcinoma were detected by immunohistochemitry. The mRNA of FasL was measured by in situ hybridization in the consecutive tissue slices of 80 colorectal carcinomas respectively. Using terminal deoxynucleotidyl transferase-mediaed dUTP nick end labeling （TUNEL）, apoptotic cells were detected in 80 specimens of colorectal carcinoma. The expression of FasL was detected in all 80 specimens, but it was not even in the same or among different tissues. In the consecutive tissue slices, the location of expression of FasL protein corresponded with that of FasL mRNA. In those with FasL extensive expression, the number of TILs was less than that of FasL weak expression （P〈0. 05）, and the apoptotic index （AI） of TILs was higher and that of tumor cells was lower than that of FasL with weak expression respectively （P〈0. 01）. The AI of TILs was correlated with that of tumor cells （r=-0. 631, P〈0. 01）. It was suggested that colorectal carcinoma cells can induce the apoptosis of TILs through the expression of FasL, which can counterattack the immune system. This may be one of the mechanisms of immune evasion in colorectal carcinoma.

Apoptosis and Fas System Are Significantly Involved in the Process of Liver Cirrhosis Converting into Hepatocellular Carcinoma

To investigate the roles of apoptosis and the Fas system in the process of liver cirrhosis converting into hepatocellular carcinoma , expression of Fas and Fas ligand in 49 LC and 36 HCC samples was detected by immunohistochemical method. Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling method. Serum soluble Fas levels in 28 cases of LC and 27 cases of HCC were measured by enzyme linked immunosorbent assay method. Compared with LC, apoptotic indices in HCC tissues were significantly reduced , expression of Fas was decreased , and that of FasL was increased . Serum sFas levels in HCC patients were significantly higher than those in normal controls. Down regulation of Fas expression, up regulation of FasL expression in hepatocytes and elevation of sFas level in serum might contribute to tumor escape from immune surveillance of the body. Apoptosis and the Fas system are significantly involved in the process of liver cirrhosis converting into hepatocellular carcinoma.

The Effect of the Fas/FasL Pathway during Chemotherapeutic Drug-induced Apoptosis of Leukameic Cells

The mechanism of chemotherapeutic drug-induced apoptosis in leukaemic cells was studied to further investigate whether Fas/FasL system was involved in apoptosis induced by chemotherapeutic drugs and assess their effects when used in combination with soluble FasL (sFasL). The expression of Fas on human leukaemic cell lines K562, HL-60 and U937 treated with daunorubicin (DNR) or cytosine arabinoside (Ara-C) was detected by using flow cytometry. The activities of sFasL, DNR and Ara-C inducing apoptosis of leukaemic cells, in the absence or presence of neutralizing anti-Fas IgG antibody, were detected by using flow cytometry and TUNEL. The results showed that flow cytometric profiles of K562, HL-60 and U937 cells treated with DNR or Ara-C failed to show any significant increase in Fas expression over 18 h (P>0.05). Anti-Fas monoclonal antibody (IgG) could not block the apoptosis in leukaemic cells induced by DNR or Ara-C, but could block the apoptosis induced by sFasL. A role of sFasL in a cytotoxic synergistic effect when used in combination with chemotherapeutic drugs was revealed. It was concluded that chemotherapeutic drug-induced apoptosis in human leukaemic cells (UG37, HL-60) is independent of the Fas/FasL system, but combination of sFasL and drug treatment produces a synergistic cytotoxic effect on human luekaemic cells.

The expression of Fas, FasL and their biological behavior in human cervical carcinoma

Objective： To investigate the relationship between the expression of Fas and Fas ligand （FasL） and its biological behavior in human cervix carcinoma. Methods： Immunohistochemisty technique was used to detect the expression of Fas and FasL in 47 cases of cervical carcinoma, 16 cases of cervical interaepithelial neoplasia, 10 cases of chronic cervicitis and 10 cases of normal cervix. TUNEL technique was used to observe the apoptic cells in 47 cases of cervical carcinoma. Retrospective study was carried out to find the relationship between the expression of Fas and FasL and cell apoptosis, clinical stage, pathological classification, lymph node metastasis, prognosis and age. Results： The expression of Fas and FasL was significantly different in different cervix （P 〈 0.01）, and also related to the degree of differentiation, lymph node metastasis and prognosis （P 〈 0.05）. But had no relation with clinical stage or age （P 〉 0.05） ; Cervix carcinoma cells apoptosis in different pathological classification appeared negative relation （Rs=-0.35, P 〈 0.05 ）. Cervix carcinoma cell apoptosis was significantly higher in Fas-positive and FasL- positive than that in Fas-negative and FasL-negative （P 〈 0.05）. By retrospective investigation, Fas-negative and FasL-positive were related to poor prognoses of the patients with cervical carcinoma （P 〈 0.05 ）. Conclusion： The development of apoptosis in cervix carcinoma has a promoting regulation function in Fas and FasL expression. Gene treatment can alter apoptosis abnormality, thus induce apoptosis in cancerous cell expressing Fas and FasL. Fas or FasL may be taken as a marker in the prognostic character- ization.

Selective Depletion of the Allo-Antigen Specific T Cells by Fas/FasL Pathway by Cytokine IFN-γ and IL-2

To investigate the value of apoptosis of the allo antigen specific T cells induced by Fas/FasL pathway in preventing graft versus host disease (GVHD), the CD34 + cells transfected with FasL or not, used as stimulus cells, were mixed with allo antigen specific T lymphocytes in presence or absence of IFN γand IL 2. After 5 days, apoptosis of T cells was detected by TdT nick end mediated dUTP labeling (TUNEL) and flow cytometry (FCM). The affects of these two cytokines on CD34 + cells in the graft were also compared. The ratio of apoptosis of T cells was 12.1±1.5 % when CD34 + cells transfected with FasL was used as stimulus cells, much higher than that of CD34 + cells non transfected (3.2 ±1.1 %, P <0.01). And in presence of IFN γ or IL 2, the ratio reached 20.1±2.3 %, 17.6±1.3 % respectively ( P <0.01). However, IFN γ up regulated Fas expression of CD34 + cells and increased the sensibility of CD34 + cells to soluble FasL(sFasL); IL 2 showed no such affect. It is possible to induce apoptosis of the allo antigen specific T cells of grafts activated by allo antigen by exogenous Fas ligand expressed on recipient cells and this might provide a new approach for preventing GVHD and IL 2 may be more suitable for clinical application.

The effect of FasL gene transfer to islet cells on pancreatic islet allografts

OBJECTIVE: To investigate the effect of FasL gene transfer to islet cells on pancreatic islet allografts. METHODS: A recombinant and replication-deficient type-5 adenovirus encoding murine FasL (AdV- FasL) was constructed by the method of calcium phosphate precipitation. Pancreatic islets were infected with the recombinant adenovirus AdV-FasL, and transplanted into diabetic recipients. FasL expression was detected by RT-PCR and immunohistochemistry. The survival of allografts and the apoptosis of gene transferred islet allografts were analyzed. RESULTS: All animals receiving islet allograft alone returned to a diabetic state by several days (mean survival time 6.3±0.6 days). Compared with the control group, no delayed rejection and prolonged survival of allografts were observed in the group of FasL gene transfer. The rejection was accelerated and the allograft survival was shortened to 3.4±0.2 days (P<0.05). Pancreatic islets infected with AdV- FasL demonstrated positive staining of FasL at 24 h, with an increased intensity at 48 h, but not in AdV-5 infected or uninfected islets. TUNEL labeling of pancreatic islet allografts at 24, 48 h revealed apoptosis that was not in AdV-5 infected allografts. CONCLUSIONS: Though co-transplantation of FasL-expressing testicular cells can induce privilege of islet allografts and prolong allograft survival, direct expression of FasL on islet allografts infected with AdV-FasL may accelerate islets rejection by islet apoptosis and granulocyte infiltration.

Attenuation of GVHD for Allo-Bone Marrow Transplantation Recipient by FasL-Fas Pathway in an H-2 Haplotype Disparate Mouse Combination

In order to explore a new special and effective way to prevent graft versus host disease (GVHD) after allogenic bone marrow transplantation (allo-BMT), the stem cell antigen-1 (Sca-1) + early hematopoietic cells (EHC) from BALB/c mouse (H-2 d) were introduced with exogenous mouse Fas ligand (mFasL) cDNA gene by the retrovirus-mediated gene transfer and expanded for one week, and then they were co-cultured with the spleen mononuclear cells (SMNC) from BAC mouse (H-2 d×b) as one way mixed lymphocyte reaction (OWMLR). The cytotoxicity of treated BAC mouse SMNC against Na 2 51CrO 4 labeling SMNC from BALB/c mouse was observed. The bone marrow mononuclear cells (BMMNC) from BAC mouse treated by the above methods were transplanted into lethally-irradiated congenic BALB/c mice to observe the occurrence of GVHD. The results showed that the SMNC from BAC mouse after OWMLR with exogenous mFasL cDNA gene-transduced hematopoietic cells (HC) from BALB/c mouse in a ratio of 1 to 5 exhibited an obvious inhibition of the cytotoxicity against the BALB/c mouse spleen cells at different effector/target ratios as compared to the control group (P<0.01). The gradeⅠ GVHD or no GVHD and the 80 % survival rate at day 60 post-BMT were observed in the BALB/c mouse receiving BAC mouse BMMNC treated with similar way, while the grade Ⅱ-Ⅲ GVHD and the 20 % survival rate were noted in the control group (P<0.01). It is suggested that the attenuation of GVHD in allo-BMT recipient could be successfully achieved through FasL-Fas pathway in an H-2 haplotype disparate mouse combination.