CD4+ T cells are trigger and target of the glucocorticoid response that prevents lethal immunopathology in toxoplasma infection.
J Exp Med
; 210(10): 1919-27, 2013 Sep 23.
Article
en En
| MEDLINE
| ID: mdl-23980098
ABSTRACT
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 (GR(lck-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 GR(lck-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 GR(lck-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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Toxoplasma
/
Linfocitos T CD4-Positivos
/
Toxoplasmosis
/
Glucocorticoides
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2013
Tipo del documento:
Article