The low affinity t of ABT 737 in A1, a selection of antigen-specific T cells was determined in the first days after activation. Alvespimycin 17-DMAG This explains Rt why ABT 737 is not effective as an immunosuppressant in the first days after transplantation and acute phase an autoimmune disease, 20 years, but the clinical use of induction therapy prior to solid organ or stem cell found. However, we believe that the opposite result with a selective inhibitor of A1 would be obtained, but none of the currently available inhibitors of Bcl-2 selectively binds to A1.

The fact that ABT 737 effectively destroyed in combination with CsA rt T cells activated in a GvHD model HvG and starts Rt synergistic effect of ABT 737 and CsA, as we observed previously in a model of skin graft, and 19 to raise a reasonable M possibility, the immunosuppressive effect of Bcl-2 inhibitors.
Close it Lich unique selectivity t profile of ABT 737, you will find a useful application for cell-based immunotherapy. Experimental selection of antigen-specific cells after a short activation time is difficult and limited largely to the use ATPase of transgenic systems. ABT 737 is used to select antigen-specific polyclonal cells after antigen recognition in vitro and in vivo auszuw, Wherein a broad application in the field of experimental infection and cancer immunology, which, for the production of viral or tumor-antigen-specific T of MHC presented the h You. As resistance ABT h 737 depends Only by an activation signal, k Can antigen-specific T-cells are further ILS influenced for generating particular subsets of T cells in vitro, such as regulatory T cells or donorreactive CMV-reactive cytotoxic T cells .
32 Thus, in this study, we have described for the first time, characterized, and found a way to get the resistance to ABT 737 to overcome in activated T cells. In addition, we propose a link between resistance to ABT 737 in established tumor cells and physiological lymphocyte activation after antigen recognition. These results are relevant to an m Possible clinical application of the Bcl-2 inhibitors as an immunomodulator and cytostatic drugs. Materials and Methods Mouse. C57BL / 6, CBA, F1, and BM3. Mice 3 M Were under conditions free of specific pathogens at the University of t placed too rich . The BM3. Mice At 3, 33, all expressing transgenic TCR CD8 T cells of a naturally processed octapeptide selectively bound to the allogeneic MHC class I molecule H 2 K, was kindly provided by AM Schmitt Verhulst.
34 All animal experiments were carried out according to protocols approved by the Court. Synchimeras and model of the GVH reaction. Synchimeric animals were generated as previously described. 35.36 In short, 5_106 bone marrow cells from BM3. Mice 3 M Were in Mice injected CBA na Ves with 3 Gy irradiated transplanted the same day. After 6 0 weeks, were injected with B6 splenocytes, and treatment with ABT 737) or vehicle was cozy the experimental protocol initiated. Reactive donor BM3. 3 CD8 T cells were detected in blood using the antique Rpers Ti98, which selectively stored in the BM3. 3 TCR. 37 GVH reactions were studied in a model parent in Formula 1. F1 Mice were breeding females of the CBA and B6 M Nnchen be generated, and U Erte H 2k and H 2b. After adoptive transfer of 20 5_106 BM3. 3 splenocytes GVHR