Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-gamma)-producing CD45RC(+) RT6(-) T helper cells

被引:25
作者
Beijleveld, LJJ
Groen, H
Broeren, CPM
Klatter, FA
Kampinga, J
Damoiseaux, JGMC
Vriesman, PJCV
机构
[1] UNIV LIMBURG, FAC MED, DEPT IMMUNOL, NL-6200 MD MAASTRICHT, NETHERLANDS
[2] UNIV GRONINGEN, FAC MED, DEPT HISTOL & CELL BIOL, GRONINGEN, NETHERLANDS
[3] UNIV UTRECHT, FAC VET MED, INST INFECT DIS & IMMUNOL, UTRECHT, NETHERLANDS
关键词
rat Th1 and Th2 cells; thymus; autoimmunity; cycloeporine;
D O I
10.1046/j.1365-2249.1996.d01-797.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 mononuclear cell subsets phenotypically by tri-colour flow cytometry. A strong decrease in recent thymic emigrants (Thy1.1(+), TCR alpha beta(+)) 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 of CsA-AI; CD4(+) and CD8(+) cells consisted predominantly of monocytes (CD4(dim+), TCR alpha beta(-)) and natural killer cells (CD8(+), TCR alpha beta(-)), 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-gamma upon stimulation, and therefore were considered as Th1-like effector cells. These results are consistent with the view that a persistent preponderance of Th1 cells and not the mere presence of autoreactive cells determines whether or not clinically manifest CsA-AI will occur.
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收藏
页码:486 / 496
页数:11
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