GM-CSF restores innate, but not adaptive, immune responses in glucocorticoid-immunosuppressed human blood in vitro

Jian Xu, Rudolf Lucas, Marcus Schuchmann, Simone Kühnle, Thomas Meergans, Ana P. Barreiros, Ansgar W. Lohse, Gerd Otto, Albrecht Wendel

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Infection remains the major complication of immunosuppressive therapy in organ transplantation. Therefore, reconstitution of the innate immunity against infections, without activation of the adaptive immune responses, to prevent graft rejection is a clinically desirable status in transplant recipients. We found that GM-CSF restored TNF mRNA and protein expression without inducing IL-2 production and T cell proliferation in glucocorticoid-immunosuppressed blood from either healthy donors or liver transplant patients. Gene array experiments indicated that GM-CSF selectively restored a variety of dexamethasone-suppressed, LPS-inducible genes relevant for innate immunity. A possible explanation for the lack of GM-CSF to restore T cell proliferation is its enhancement of the release of IL-1βR antagonist, rather than of IL-1β itself, since exogenously added IL-1β induced an IL-2-independent Con A-stimulated proliferation of glucocorticoid-immunosuppressed lymphocytes. Finally, to test the in vivo relevance of our findings, we showed that GM-CSF restored the survival of dexamethasone- or cyclosporine A-immunosuppressed mice from an otherwise lethal infection with Salmonella typhimurium. In addition to this increased resistance to infection, GM-CSF did not induce graft rejection of a skin allotransplant in cyclosporine A-immunosuppressed mice. The selective restoration potential of GM-CSF suggests its therapeutic use in improving the resistance against infections upon organ transplantation.

Original languageEnglish (US)
Pages (from-to)938-947
Number of pages10
JournalJournal of Immunology
Volume171
Issue number2
DOIs
StatePublished - Jul 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'GM-CSF restores innate, but not adaptive, immune responses in glucocorticoid-immunosuppressed human blood in vitro'. Together they form a unique fingerprint.

  • Cite this

    Xu, J., Lucas, R., Schuchmann, M., Kühnle, S., Meergans, T., Barreiros, A. P., Lohse, A. W., Otto, G., & Wendel, A. (2003). GM-CSF restores innate, but not adaptive, immune responses in glucocorticoid-immunosuppressed human blood in vitro. Journal of Immunology, 171(2), 938-947. https://doi.org/10.4049/jimmunol.171.2.938