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 Citations (Scopus)

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

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Adaptive Immunity
Granulocyte-Macrophage Colony-Stimulating Factor
Glucocorticoids
Infection
Graft Rejection
Organ Transplantation
Interleukin-1
Innate Immunity
Dexamethasone
Cyclosporine
Interleukin-2
Cell Proliferation
T-Lymphocytes
Therapeutic Uses
Salmonella typhimurium
Immunosuppressive Agents
Genes
In Vitro Techniques
Tissue Donors
Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

GM-CSF restores innate, but not adaptive, immune responses in glucocorticoid-immunosuppressed human blood in vitro. / Xu, Jian; Lucas, Rudolf; Schuchmann, Marcus; Kühnle, Simone; Meergans, Thomas; Barreiros, Ana P.; Lohse, Ansgar W.; Otto, Gerd; Wendel, Albrecht.

In: Journal of Immunology, Vol. 171, No. 2, 15.07.2003, p. 938-947.

Research output: Contribution to journalArticle

Xu, J, Lucas, R, Schuchmann, M, Kühnle, S, Meergans, T, Barreiros, AP, Lohse, AW, Otto, G & Wendel, A 2003, 'GM-CSF restores innate, but not adaptive, immune responses in glucocorticoid-immunosuppressed human blood in vitro', Journal of Immunology, vol. 171, no. 2, pp. 938-947. https://doi.org/10.4049/jimmunol.171.2.938
Xu, Jian ; Lucas, Rudolf ; Schuchmann, Marcus ; Kühnle, Simone ; Meergans, Thomas ; Barreiros, Ana P. ; Lohse, Ansgar W. ; Otto, Gerd ; Wendel, Albrecht. / GM-CSF restores innate, but not adaptive, immune responses in glucocorticoid-immunosuppressed human blood in vitro. In: Journal of Immunology. 2003 ; Vol. 171, No. 2. pp. 938-947.
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