Alloantigen-induced, T-cell-dependent production of nitric oxide by macrophages infiltrating skin allografts in mice
Language English Country Switzerland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Time Factors MeSH
- DNA Primers MeSH
- Transplantation, Homologous immunology MeSH
- Immunosuppression Therapy methods MeSH
- Isoantigens immunology MeSH
- Kinetics MeSH
- Coculture Techniques MeSH
- Lymph Nodes cytology MeSH
- Lymphocyte Depletion MeSH
- Macrophages cytology immunology MeSH
- Mice, Inbred A MeSH
- Mice, Inbred BALB C MeSH
- Mice, Inbred C57BL MeSH
- Mice, Inbred DBA MeSH
- Mice MeSH
- Nitric Oxide biosynthesis MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Base Sequence MeSH
- Nitric Oxide Synthase Type II MeSH
- Nitric Oxide Synthase genetics MeSH
- T-Lymphocytes immunology MeSH
- Transplantation, Isogeneic immunology MeSH
- Skin Transplantation immunology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA Primers MeSH
- Isoantigens MeSH
- Nos2 protein, mouse MeSH Browser
- Nitric Oxide MeSH
- Nitric Oxide Synthase Type II MeSH
- Nitric Oxide Synthase MeSH
The immunological rejection reaction occurring after organ or tissue transplantation is characterized by a strong infiltration of the graft by T cells and macrophages. Since the rejection reaction is highly specific, we tested the role of T cells in the activation of macrophages and in the induction of nitric oxide (NO) production during graft rejection. The rejection of both MHC and non-MHC antigen-disparate skin allografts was associated with a significantly increased production of NO in the graft. The kinetics of NO production after transplantation correlated with the rejection reaction and with the fate of the allograft. A significant reduction in NO production was found in immunologically hyporeactive mice treated with cyclosporine, and no specific production of NO was found in tolerated skin allografts from neonatally tolerant mice. The production of NO was completely suppressed in graft explants from mice with depleted CD4(+) cells, but remained at a normal level in skin allografts from mice treated with anti-CD8 monoclonal antibody. The treatment of recipients of fully allogeneic skin grafts with 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a specific inhibitor of the inducible NO synthase, resulted in a significant prolongation of graft survival. The results thus show CD4(+) T-cell-dependent, alloantigen-induced production of NO by graft-infiltrating macrophages and the role of NO in the rejection reaction. We suggest that this pathway may represent one of the local effector mechanisms of graft rejection.
References provided by Crossref.org
Prevention of corneal allograft rejection in a mouse model of high risk recipients
