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The BH3-mimetic ABT-737 inhibits allogeneic immune responses
- Source :
- Transplant International. 24:722-732
- Publication Year :
- 2011
- Publisher :
- Frontiers Media SA, 2011.
-
Abstract
- Summary Apoptosis controls the adaptive immune system through regulation of central and peripheral lymphocyte deletion. Therefore, substances that selectively interact with the intrinsic apoptosis pathway in lymphocytes offer unexplored opportunities to pharmacologically modulate the immune response. Here, we present evidence that the BH3-mimetic ABT-737 suppresses allogeneic immune responses. In vitro, ABT-737 prevented allogeneic T-cell activation, proliferation, and cytotoxicity by apoptosis induction, but without impairing the physiological functions of remaining viable T cells. In vivo, ABT-737 was highly selective for lymphoid cells and inhibited allogeneic T- and B-cell responses after skin transplantation. The immunosuppressive effect of ABT-737 was markedly increased in combination with low-dose cyclosporine A, as shown by the induction of long-term skin graft survival without significant inflammatory infiltrates in 50% of the recipients in an MHC class I single antigen mismatched model. Thus, pharmacological targeting of Bcl-2 proteins represents a novel immunosuppressive approach to prevent rejection of solid organ allografts.
- Subjects :
- 0303 health sciences
Transplantation
BH3 Mimetic ABT-737
biology
business.industry
medicine.medical_treatment
Lymphocyte
Intrinsic apoptosis
Immunosuppression
Acquired immune system
3. Good health
03 medical and health sciences
0302 clinical medicine
Immune system
medicine.anatomical_structure
Antigen
MHC class I
Immunology
biology.protein
Medicine
business
030304 developmental biology
030215 immunology
Subjects
Details
- ISSN :
- 09340874
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Transplant International
- Accession number :
- edsair.doi...........8deafb04de4cd6dfb7005ba7de766cd1