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

Ashraful Haque; Amanda C Stanley; Fiona H Amante; Fabian de Labastida Rivera; Yonghong Zhou; Rachel D Kuns; Vanessa Yardley; Shimon Sakaguchi; Geoffrey R Hill; Christian R Engwerda; (2010) Therapeutic glucocorticoid-induced TNF receptor-mediated amplification of CD4+ T cell responses enhances antiparasitic immunity. Journal of immunology (Baltimore, Md, 184 (5). pp. 2583-2592. ISSN 0022-1767 DOI: 10.4049/jimmunol.0903080
Copy

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-gamma, 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.

Full text not available from this repository.

Atom BibTeX OpenURL ContextObject in Span Multiline CSV OpenURL ContextObject Dublin Core Dublin Core MPEG-21 DIDL EndNote HTML Citation JSON MARC (ASCII) MARC (ISO 2709) METS MODS RDF+N3 RDF+N-Triples RDF+XML RIOXX2 XML Reference Manager Refer Simple Metadata ASCII Citation EP3 XML
Export

Downloads