Glucocorticoid-Induced TNFR-Related Protein Stimulation Reverses Cardiac Allograft Acceptance Induced by CD40-CD40L Blockade
Joint Authors
Csencsits-Smith, Keri
Krill, Kenneth T.
Faust, Susan
Bishop, D. Keith
Lu, Guanyi
Wood, Sherri C.
Source
Clinical and Developmental Immunology
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-04-17
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
CD40-CD40L blockade has potent immunosuppressive effects in cardiac allograft rejection but is less effective in the presence of inflammatory signals.
To better understand the factors that mediate CD40-CD40L blockade-resistant rejection, we studied the effects of stimulation through glucocorticoid-induced TNFR-related protein (GITR), a costimulatory protein expressed by regulatory and effector T cells.
Stimulation of CD40−/− or wild-type recipient mice treated with anti-CD40L mAb (WT+anti-CD40L) and with agonistic anti-GITR mAb resulted in cardiac allograft rejection.
GITR stimulation did not induce rejection once long-term graft acceptance was established.
In vitro, GITR stimulation increased proliferation of effector T cells and decreased regulatory T cell (Treg) differentiation in both treatment groups.
GITR-stimulated CD40−/− recipients rejected their allografts more rapidly compared to GITR-stimulated WT+anti-CD40L recipients, and this rejection, characterized by a robust Th2 response and significant eosinophilic infiltrate, could be mediated by CD4+ T cells alone.
In contrast, both CD4+ and CD8+ T cells were required to induce rejection in GITR-stimulated WT+anti-CD40L-treated recipients, and the pathology of rejection was less severe.
Hence, early GITR stimulation could initiate graft rejection despite CD40 deficiency or anti-CD40L mAb treatment, though the recipient response was dependent on the mechanism of CD40-CD40L disruption.
American Psychological Association (APA)
Krill, Kenneth T.& Csencsits-Smith, Keri& Wood, Sherri C.& Faust, Susan& Lu, Guanyi& Bishop, D. Keith. 2013. Glucocorticoid-Induced TNFR-Related Protein Stimulation Reverses Cardiac Allograft Acceptance Induced by CD40-CD40L Blockade. Clinical and Developmental Immunology،Vol. 2013, no. 2013, pp.1-9.
https://search.emarefa.net/detail/BIM-513849
Modern Language Association (MLA)
Krill, Kenneth T.…[et al.]. Glucocorticoid-Induced TNFR-Related Protein Stimulation Reverses Cardiac Allograft Acceptance Induced by CD40-CD40L Blockade. Clinical and Developmental Immunology No. 2013 (2013), pp.1-9.
https://search.emarefa.net/detail/BIM-513849
American Medical Association (AMA)
Krill, Kenneth T.& Csencsits-Smith, Keri& Wood, Sherri C.& Faust, Susan& Lu, Guanyi& Bishop, D. Keith. Glucocorticoid-Induced TNFR-Related Protein Stimulation Reverses Cardiac Allograft Acceptance Induced by CD40-CD40L Blockade. Clinical and Developmental Immunology. 2013. Vol. 2013, no. 2013, pp.1-9.
https://search.emarefa.net/detail/BIM-513849
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-513849