An Immunomodulatory Role for Follistatin‐Like 1 in Heart Allograft Transplantation
| Autor: | P. Thebault, Cedric Louvet, J. B. Le Luduec, Michèle Heslan, Elise Chiffoleau, Thomas Condamine, Maria-Cristina Cuturi, J.-M. Heslan |
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| Rok vydání: | 2008 |
| Předmět: |
Follistatin-Related Proteins
medicine.medical_treatment Oligonucleotides CD8-Positive T-Lymphocytes Proinflammatory cytokine Rats Sprague-Dawley Interferon-gamma In vivo medicine Animals Transplantation Homologous Immunology and Allergy Pharmacology (medical) Heart transplantation Transplantation biology Interleukin-6 business.industry Interleukin-17 Gene Transfer Techniques Nucleic Acid Hybridization Dendritic Cells Rats surgical procedures operative Rats Inbred Lew Suppression subtractive hybridization Immunology Circulatory system biology.protein Heart Transplantation business CD8 Follistatin |
| Zdroj: | American Journal of Transplantation. 8:2297-2306 |
| ISSN: | 1600-6135 |
| Popis: | Donor-specific tolerance to heart allografts in the rat can be achieved by donor-specific blood transfusions (DST) before transplantation. We have previously reported that this tolerance is associated with strong leukocyte infiltration, and that host CD8(+) T cells and TGFbeta are required. In order to identify new molecules involved in the induction phase of tolerance, we compared tolerated and rejected heart allografts (suppressive subtractive hybridization) 5 days after transplantation. We identified overexpression of Follistatin-like 1 (FSTL1) transcript in tolerated allografts compared to rejected allografts or syngeneic grafts. We show that FSTL1 is overexpressed during both the induction and maintenance phase of tolerance, and appears to be specific to the tolerance model induced by DST. Analysis of graft-infiltrating cells revealed predominant expression of FSTL1 in CD8(+) T cells from tolerated grafts, and depletion of these cells prior to transplantation abrogated FSTL1 expression and heart allograft survival. Moreover, overexpression of FSTL1 by adenovirus gene transfer in vivo significantly prolonged allograft survival in association with inhibition of the proinflammatory cytokines, IL6, IL17 A and IFNgamma. Taken together, these results suggest that FSTL1 could be an active component of the mechanisms mediating heart allograft tolerance. |
| Databáze: | OpenAIRE |
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