Selective depletion of the allo-antigen specific T cells by Fas/FasL pathway by cytokine IFN-gamma 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-gamma and 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-gamma or IL-2, the ratio reached 20.1+/-2.3%, 17.6+/-1.3% respectively (P<0.01). However, IFN-gamma up-regulated Fas expression of CD34+ cells and increased the sensibility of CD34+ cells to soluble FasL (sFasL); IL-2 showed no such effect. 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.
Xiao
Juan
J
The Institute of Hematology, Xiehe Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430022.
Zou
Ping
P
Liu
Zhongwen
Z
Liu
Lingbo
L
Hu
Zhongbo
Z
D018952:Antigens, CD34 / Q000096:biosynthesis / Q000276:immunology; D017209:Apoptosis; D003602:Cytotoxicity, Immunologic; D018076:DNA, Complementary / Q000235:genetics; D053222:Fas Ligand Protein; D006086:Graft vs Host Disease / Q000517:prevention & control; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology
D018952:Antigens, CD34; D018076:DNA, Complementary; D053222:Fas Ligand Protein; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D019014:fas Receptor; D007371:Interferon-gamma