Flt-3 ligand increases microchimerism but can prevent the therapeutic effect of donor bone marrow in transiently immunosuppressed cardiac allograft recipients
| Autor: | M A, Antonysamy, R J, Steptoe, A, Khanna, W A, Rudert, V M, Subbotin, A W, Thomson |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Mice Inbred C3H Transplantation Conditioning Base Sequence Chimera T-Lymphocytes Genes MHC Class II Graft Survival Histocompatibility Antigens Class II Membrane Proteins Lymphocyte Activation Polymerase Chain Reaction Tacrolimus Tissue Donors Mice Inbred C57BL Mice Transplantation Isogeneic Animals Heart Transplantation Immunosuppressive Agents Bone Marrow Transplantation DNA Primers |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 160(8) |
| ISSN: | 0022-1767 |
| Popis: | C3H (H2k) mice received 50 x 10(6) B10 (H2b) bone marrow (BM) cells either alone or with flt-3 ligand (FL) (10 microg/day), tacrolimus (2 mg/kg/day), or both agents for 7 days. Donor MHC class II+ (IAb+) cells were quantitated in spleens by immunohistochemical analysis, and donor class II DNA detected in BM by PCR. Donor cells were rare in the BM alone and BM + FL groups, whereas there was a substantial increase in chimerism in the BM + tacrolimus group. Addition of FL to BM + tacrolimus led to a further eightfold increase in donor cells and enhanced donor DNA compared with the BM + tacrolimus group. This increase in donor cells was almost 500-fold compared with BM alone. C3H recipients of B10 heart allografts given perioperative B10 BM and tacrolimus (days 0-13) exhibited a markedly extended median graft survival time (MST, 42 days) compared with those given tacrolimus alone (MST, 22 days). Addition of FL (10 microg/day; 7 days) to BM + tacrolimus prevented the beneficial effect of donor BM (MST, 18 days). BM alone or BM + FL resulted in uniform early heart graft failure (MST8 days). Functional studies revealed maximal antidonor MLR and CTL activities in the BM- and BM + FL-treated groups, with minimal activity in the tacrolimus-treated groups. Thus, dramatic growth factor-induced increases in chimerism achieved under cover of immunosuppression may result in augmented antidonor T cell reactivity and reduced graft survival after immunosuppressive drug withdrawal. With FL, this may reflect striking augmentation of immunostimulatory dendritic cells. |
| Databáze: | OpenAIRE |
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