Statements in which the resource exists as a subject.
PredicateObject
rdf:type
pubmed:issue
1
pubmed:dateCreated
2001-6-20
pubmed:abstractText
The use of the immunosuppressive drug cyclosporine A (CsA) in solid organ transplantation can be associated with the development of vasculopathy as part of the complex immune response involved in chronic rejection, including autoimmune recognition. Although CsA can directly affect endothelial cells, this drug alters the T cell repertoire promoting autoimmune recognition. The present studies evaluated the ability of CsA-induced autoreactive T cells to mediate vascular lesions in syngeneic heart grafts. Graft vasculopathy developed in syngeneic heart grafts following either the primary induction of autoimmunity with CsA or the adoptive transfer of CsA-induced autoreactive T cells. Initially, an inflammatory response occurred in the medial wall of the small arterial vessels, accompanied by a perivascular lymphocytic infiltrate (including a lymphocytic infiltrate into the myocardium), followed by progression of vascular disease with endothelial cell proliferation. The development and progression of vascular disease correlated with the cytokine profile of the infiltrating lymphocytes with type 1 cytokines detected early and type 2 cytokines detected as the disease progressed. Initiation of this response correlated with upregulation of the target antigen recognized by the CsA-induced autoreactive T cells, the MHC class II-invariant chain peptide complex. This antigen complex, when upregulated on endothelial cells by interferon, allowed effective targeting by the autoreactive T lymphocytes. Strategies to inhibit the upregulation of MHC class II antigens by treatment of the recipients with chloroquine truncated the disease process. The results of these studies suggest that CsA-induced autoreactive mechanisms can contribute to the development of graft vasculopathy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1521-6616
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
57-70
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11414746-Adoptive Transfer, pubmed-meshheading:11414746-Animals, pubmed-meshheading:11414746-Antigens, Differentiation, B-Lymphocyte, pubmed-meshheading:11414746-Arteriosclerosis, pubmed-meshheading:11414746-Autoimmune Diseases, pubmed-meshheading:11414746-Chloroquine, pubmed-meshheading:11414746-Cyclosporine, pubmed-meshheading:11414746-Cytotoxicity, Immunologic, pubmed-meshheading:11414746-Disease Progression, pubmed-meshheading:11414746-Female, pubmed-meshheading:11414746-Graft Rejection, pubmed-meshheading:11414746-Graft vs Host Disease, pubmed-meshheading:11414746-Heart Transplantation, pubmed-meshheading:11414746-Histocompatibility Antigens Class II, pubmed-meshheading:11414746-Immunosuppressive Agents, pubmed-meshheading:11414746-Lymphocyte Depletion, pubmed-meshheading:11414746-Lymphokines, pubmed-meshheading:11414746-Macromolecular Substances, pubmed-meshheading:11414746-Postoperative Complications, pubmed-meshheading:11414746-Radiation Chimera, pubmed-meshheading:11414746-Rats, pubmed-meshheading:11414746-Rats, Inbred Lew, pubmed-meshheading:11414746-T-Lymphocytes, pubmed-meshheading:11414746-Th1 Cells, pubmed-meshheading:11414746-Th2 Cells, pubmed-meshheading:11414746-Thymectomy, pubmed-meshheading:11414746-Transplantation, Isogeneic, pubmed-meshheading:11414746-Tunica Intima, pubmed-meshheading:11414746-Tunica Media, pubmed-meshheading:11414746-Vasculitis
pubmed:year
2001
pubmed:articleTitle
Autoimmune-mediated vasculopathy.
pubmed:affiliation
Department of Oncology, The Johns Hopkins University, Baltimore, Maryland 21231, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.