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Neutralizing interleukin-4 prevents transplant arteriosclerosis mediated by indirect pathway T cells under CD40-CD154 costimulation blockade.
- Source :
-
Transplantation [Transplantation] 2008 Dec 15; Vol. 86 (11), pp. 1615-21. - Publication Year :
- 2008
-
Abstract
- Introduction: Blockade of the CD40-CD154 costimulatory pathway can prolong allograft survival, but does not prevent the development of transplant arteriosclerosis in several models. In this study, we investigated the mechanisms of CD40-CD154-independent transplant arteriosclerosis in major histocompatibility complex (MHC)-class I-mismatched aortic allografts.<br />Methods: MHC class I-mismatched CBK (H2k+Kb) donor aortas were transplanted into CBA (H2k) recipients who can only recognize the graft through CD8+ T cells and CD4+ T cells responding to the class I MHC mismatch through the indirect pathway of allorecognition. Recipients were treated with anti-CD154 antibody (MR1) alone or in combination with anti-CD8 (YTS169) or anti-interleukin (IL)-4 (11B11) antibodies. Grafts were analyzed by histology on days 30 and 60 and for intragraft mRNA expression on day 14 after transplantation.<br />Results: Repeated treatment with anti-CD154 alone or in combination with anti-CD8 antibody did not prevent intimal proliferation compared with untreated controls (65%+/-6%, 62%+/-9%, and 71%+/-7% luminal occlusion, respectively, 60 days after transplantation). In both treatment groups, the expression of IL-4, IL-5, and eotaxin was increased compared with control grafts, and an eosinophilic infiltration was observed. Neutralizing IL-4 in combination with CD40-CD154 blockade and CD8+ T-cell depletion abrogated transplant arteriosclerosis (9%+/-4% luminal occlusion 60 days after transplantation).<br />Conclusion: Prolonged treatment with anti-CD154 was not able to prevent the development of transplant arteriosclerosis in MHC class I-mismatched aortic allografts, in the presence or absence of CD8+ T cells. This CD40-CD154 pathway resistant transplant arteriosclerosis was mediated by IL-4, because neutralizing IL-4 in addition to CD40-CD154 costimulation blockade and CD8+ T-cell depletion prevented its development.
- Subjects :
- Animals
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Eosinophils metabolism
Graft Survival
Histocompatibility Antigens Class I chemistry
Histocompatibility Testing
Male
Mice
Aorta transplantation
Arteriosclerosis etiology
Arteriosclerosis therapy
CD40 Antigens biosynthesis
CD40 Ligand biosynthesis
Interleukin-4 metabolism
Transplantation adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1534-6080
- Volume :
- 86
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 19077898
- Full Text :
- https://doi.org/10.1097/TP.0b013e31818bbd3a