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Glucocorticoids attenuate acute graft‐versus‐host disease by suppressing the cytotoxic capacity of CD8 + T cells
Author(s) -
TheissSuennemann Jennifer,
Jörß Katharina,
Messmann Joanna J,
Reichardt Sybille D,
MontesCobos Elena,
Lühder Fred,
Tuckermann Jan P,
AWolff Hendrik,
Dressel Ralf,
Gröne HermannJosef,
Strauß Gudrun,
Reichardt Holger M
Publication year - 2015
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4475
Subject(s) - cytotoxic t cell , cd8 , fulminant , immunology , immune system , inflammation , glucocorticoid , medicine , transplantation , t cell , adoptive cell transfer , biology , biochemistry , in vitro
Abstract Glucocorticoids ( GCs ) are released from the adrenal gland during inflammation and help to keep immune responses at bay. Owing to their potent anti‐inflammatory activity, GCs also play a key role in controlling acute graft‐versus‐host disease ( aGvHD ). Here we demonstrate that mice lacking the glucocorticoid receptor ( GR ) in T cells develop fulminant disease after allogeneic bone marrow transplantation. In a fully MHC ‐mismatched model, transfer of GR ‐deficient T cells resulted in severe aGvHD symptoms and strongly decreased survival times. Histopathological features were aggravated and infiltration of CD8 + T cells into the jejunum was increased when the GR was not expressed. Furthermore, serum levels of IL ‐2, IFNγ , and IL ‐17 were elevated and the cytotoxicity of CD8 + T cells was enhanced after transfer of GR ‐deficient T cells. Short‐term treatment with dexamethasone reduced cytokine secretion but neither impacted disease severity nor the CTLs ' cytolytic capacity. Importantly, in an aGvHD model in which disease development exclusively depends on the presence of CD8 + T cells in the transplant, transfer of GR ‐deficient T cells aggravated clinical symptoms and reduced survival times as well. Taken together, our findings highlight that suppression of CD8 + T‐cell function is a crucial mechanism in the control of aGvHD by endogenous GCs . Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.