Therapeutic glucocorticoid-induced TNF receptor-mediated amplification of CD4+ T cell responses enhances antiparasitic immunity

Haque, Ashraful, Stanley, Amanda C., Amante, Fiona H., de Labastida Rivera, Fabian, Zhou, YongHong, Kuns, Rachel D., Yardley, Vanessa, Sakaguchi, Shimon, Hill, Geoffrey R. and Engwerda, Christian R. (2010) Therapeutic glucocorticoid-induced TNF receptor-mediated amplification of CD4+ T cell responses enhances antiparasitic immunity. Journal of Immunology, 184 5: 2583-2592. doi:10.4049/jimmunol.0903080

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Author Haque, Ashraful
Stanley, Amanda C.
Amante, Fiona H.
de Labastida Rivera, Fabian
Zhou, YongHong
Kuns, Rachel D.
Yardley, Vanessa
Sakaguchi, Shimon
Hill, Geoffrey R.
Engwerda, Christian R.
Title Therapeutic glucocorticoid-induced TNF receptor-mediated amplification of CD4+ T cell responses enhances antiparasitic immunity
Formatted title
Therapeutic glucocorticoid-induced TNF receptor-mediated amplification of CD4+ T cell responses enhances antiparasitic immunity
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2010-03-01
Sub-type Article (original research)
DOI 10.4049/jimmunol.0903080
Volume 184
Issue 5
Start page 2583
End page 2592
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Collection year 2011
Language eng
Formatted abstract
Chronic infectious diseases and cancers are often associated with suboptimal effector T cell responses. Enhancement of T cell costimulatory signals has been extensively studied for cancer immunotherapy but not so for the treatment of infectious disease. The few previous attempts at this strategy using infection models have lacked cellular specificity, with major immunoregulatory mechanisms or innate immune cells also being targeted. In this study, we examined the potential of promoting T cell responses via the glucocorticoid-induced TNF receptor(GITR)family-related protein in a murine model of visceral leishmaniasis.GITR stimulation during established infection markedly improved antiparasitic immunity. This required CD4+ T cells, TNF, and IFN-γ, but crucially, was independent of regulatory T (Treg) cells. GITR stimulation enhanced CD4+ T cell expansion without modulating Treg cell function or protecting conventional CD4+ T cells from Treg cell suppression. GITR stimulation substantially improved the efficacy of a first-line visceral leishmaniasis drug against both acute hepatic infection and chronic infection in the spleen, demonstrating its potential to improve clinical outcomes. This study identifies a novel strategy to therapeutically enhance CD4+ T cell-mediated antiparasitic immunity and, importantly, achieves this goal without impairment of Treg cell function.
Copyright © 2010 by The American Association of Immunologists, Inc.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Mon, 28 Mar 2011, 09:44:43 EST by Lisa Hennell on behalf of Medicine - Royal Brisbane and Women's Hospital