A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease.
J Clin Invest
; 126(9): 3541-55, 2016 09 01.
Article
in En
| MEDLINE
| ID: mdl-27500496
ABSTRACT
Damage to the gastrointestinal tract is a major cause of morbidity and mortality in graft-versus-host disease (GVHD) and is attributable to T cell-mediated inflammation. In this work, we identified a unique CD4+ T cell population that constitutively expresses the ß2 integrin CD11c and displays a biased central memory phenotype and memory T cell transcriptional profile, innate-like properties, and increased expression of the gut-homing molecules α4ß7 and CCR9. Using several complementary murine GVHD models, we determined that adoptive transfer and early accumulation of ß2 integrin-expressing CD4+ T cells in the gastrointestinal tract initiated Th1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality. The pathogenic effect of this CD4+ T cell population critically depended on coexpression of the IL-23 receptor, which was required for maximal inflammatory effects. Non-Foxp3-expressing CD4+ T cells produced IL-10, which regulated colonic inflammation and attenuated lethality in the absence of functional CD4+Foxp3+ T cells. Thus, the coordinate expression of CD11c and the IL-23 receptor defines an IL-10-regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CD4-Positive T-Lymphocytes
/
Gastrointestinal Tract
/
Graft vs Host Disease
/
Immunologic Memory
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Clin Invest
Year:
2016
Document type:
Article