title: Susceptibility to cyclosporin A-induced autoimmunity: strain differences in relation to autoregulatory T cells.
abstract: Cyclosporin A-induced autoimmunity (CsA-AI), also called autoimmune syngeneic graft-vs-host disease, is a thymus dependent, T cell mediated rodent animal model of disease and is considered to be an experimental model for human scleroderma. Since adoptive transfer of CsA-AI by effector T cells can be prevented by autoregulatory T cells, there may also be a role for dominant tolerance in the resistance of certain rat strains to develop clinical manifest CsA-AI. LEW rats have been reported to be susceptible, whereas BN rats are resistant to CsA-AI. In the present study we first demonstrate that PVG, but not DA rats, are susceptible to CsA-AI and that disease characteristics in PVG rats are comparable to LEW rats in terms of pathogenesis and T cell kinetics, although of more rapid onset and greater severity. Next, we examined whether the relative presence of autoregulatory T-helper cells, i.e. CD25+ and/or CD45RClow CD4 T cells, is increased in resistant BN and DA rats. The results obtained reveal that the genetically determined CD45RChigh/CD45RClow ratio, but not the percentage CD25+ cells, within the CD4 T cell compartment of naïve rats is correlated with resistance to CsA-AI in these rat strains. We conclude that the relative presence of autoregulatory T cells with a CD45RClow T-helper cell phenotype may be a critical determinant in susceptibility to CsA-AI.
authors.affiliation: Department of Clinical and Experimental Immunology, University Maastricht, The Netherlands.
authors.forename: Maurits M
authors.initials: MM
authors.lastname: Barendrecht
authors.forename: Jan Willem Cohen
authors.initials: JW
authors.lastname: Tervaert
authors.forename: Peter J C
authors.initials: PJ
authors.lastname: van Breda Vriesman
authors.forename: Jan G M C
authors.initials: JG
authors.lastname: Damoiseaux
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology; D016516:CD4-CD8 Ratio; D016572:Cyclosporine / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics; D004198:Disease Susceptibility / Q000139:chemically induced / Q000276:immunology; D005260:Female; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D013934:Thymectomy; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000601:surgery
chemical_list: D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D016572:Cyclosporine; D017493:Leukocyte Common Antigens