Selective depletion of the allo-antigen specific T cells by Fas/FasL pathway by cytokine IFN-γ and IL-2

Abstract

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-γ 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-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.

Keywords

Fas ligand / CD34⁺ cells / T lymphocytes / apoptosis / graft-versus-host disease / cytokine

References

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