Open AccessSusceptibility to clinically manifest cyclosporine A (CsA)‐induced autoimmune disease is associated with interferon‐gamma (IFN‐γ)‐producing CD45RC + RT6 − T helper cells
Author(s) -
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.
Publication year - 1996
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1996.d01-797.x
Subject(s) - cd8 , immunology , t cell , cytotoxic t cell , biology , bone marrow , interferon gamma , flow cytometry , t cell receptor , autoimmune disease , immune system , antibody , in vitro , biochemistry
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 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 of CsA‐AI; CD4 + and CD8 + cells consisted predominantly of monocytes (CD4 dim+ , 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 cells and not the mere presence of autoreactive cells determines whether or not clinically manifest CsA‐AI will occur.