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- Title
Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-γ)--producing CD45RC<sup>+</sup> RT6¯ T helper cells.
- Authors
Beijleveld, L. J. J.; Groen, H.; Broeren, C. P. M.; Klatter, F. A.; Kampinga, J.; Damoiseaux, J. G. M. C.; van Breda Vriesman, P. J. C.
- Abstract
Lethally irradiated Lewis (LEW) rats reconstituted with syngeneic bone marrow and given CsA for a 4-week period, develop, upon withdrawal of CsA, a graft-versus-host-like disease, so-called CsA-induced autoimmunity (CsA-AI). This T cell-mediated autoimmune disease is thymus-dependent; it is generally held that this disease is a consequence of aberrant T cell recovery brought about by CsA. In this study we determined is a consequence of aberrant T cells recovery brought about by CsA. In this study we determined mononuclear cell subsets phenotypically by tri-colour flow cytometry. A strong decrease in recent thymic emigrants (Thy 1.1 +, TCR αβ+) was observed as a consequence of CsA treatment, eventually resulting in decreased absolute peripheral T cell numbers. In these rats no altered CD4:CD8 T cell ratio was observed before onset CsA- AI: CD4+ and CD8+ cells consisted predominantly of monocytes (CD4dim+. TCR αβ+) and natural killer cells (CD8+, TCR αβ+), respectively. LEW rats, x-irradiated, syngeneic bone marrow-reconstituted and treated with CsA, showed a marked and persistent, relative expansion of mature CD45RC+, RT6- Th cells. In contrast, Brown-Norway rats treated in a similar fashion, or LEW rats subjected to either CsA treatment or x-irradiation, did not show a comparable expansion of mature CD45RC+, RT6- Th cells, nor did these animals develop CsA-AI. The CD45RC+, RT6- Th cells produced IL-2 and moreover constituted the only Th subset producing IFN-γ upon stimulation, and therefore were considered as Th1- like effector. cells. These results are consistent with the view that a persistent preponderance of Th1 and not the mere presence of autoreactive cells determines whether or not clinically manifest CsA-AI will occur.
- Subjects
AUTOIMMUNE diseases; IMMUNOLOGIC diseases; LYMPHOCYTES; AUTOIMMUNITY; ENDOCRINE glands; LYMPHOID tissue
- Publication
Clinical & Experimental Immunology, 1996, Vol 105, Issue 3, p486
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1046/j.1365-2249.1996.d01-797.x