Adachi

Alan Sher

Aliberti

Ashwell

Barrat

Bluestone

Bradley

Butcher

Chen

Cyktor

David G. Kugler

Dragana Jankovic

Franchimont

Gazzinelli

Grover

Hunter

Jamieson

Jankovic

Jonathan D. Ashwell

Liberman

Lugo-Villarino

Löwenberg

Mittelstadt

Paul R. Mittelstadt

Pérez

Roos

Schulz

Sionov

Sternberg

Tian

Villarino

Wüst

Synthetic glucocorticoids (GCs) are commonly used in the treatment of inflammatory diseases, but the role of endogenous GCs in the regulation of host-protective immune responses is poorly understood. Here we show that GCs are induced during acute Toxoplasma gondii infection and directly control the T cell response to the parasite. When infected with toxoplasma, mice that selectively lack GC receptor (GR) expression in T cells (GRlck-Cre) rapidly succumb to infection despite displaying parasite burdens indistinguishable from control animals and unaltered levels of the innate cytokines IL-12 and IL-27. Mortality in the GRlck-Cre mice was associated with immunopathology and hyperactive Th1 cell function as revealed by enhanced IFN-γ and TNF production in vivo. Unexpectedly, these CD4+ T lymphocytes also overexpressed IL-10. Importantly, CD4+ T cell depletion in wild-type or GRlck-Cre mice led to ablation of the GC response to infection. Moreover, in toxoplasma-infected RAG−/− animals, adoptive transfer of CD4+ T lymphocytes was required for GC induction. These findings establish a novel IL-10–independent immunomodulatory circuit in which CD4+ T cells trigger a GC response that in turn dampens their own effector function. In the case of T. gondii infection, this self-regulatory pathway is critical for preventing collateral tissue damage and promoting host survival.</jats:p

Crossref

The Journal of Experimental Medicine

CD4+ T cells are trigger and target of the glucocorticoid response that prevents lethal immunopathology in toxoplasma infection

http://jem.rupress.org/content/jem/210/10/1919.full.pdf

CD4+ T cells are trigger and target of the glucocorticoid response that prevents lethal immunopathology in toxoplasma infection

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