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J Immunol. 2009 Jul 1;183(1):270-6. doi: 10.4049/jimmunol.0802424. Epub 2009 Jun 12.

Blocking CD27-CD70 costimulatory pathway suppresses experimental colitis.

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  • 1Department of Pediatrics, Immune Disease Institute and Harvard Medical School, Boston, MA 02131, USA.

Erratum in

  • J Immunol. 2009 Sep 15;183(6):4135. Svend, Rietdijk [corrected to Rietdijk, Svend]; Borst, Jannine [corrected to Borst, Jannie].

Abstract

The pathogenesis of human inflammatory bowel disease (IBD) and most experimental models of IBD is dependent on the activation and expansion of CD4(+) T cells via interaction with mucosal APCs. The costimulatory receptor CD70 is transiently expressed on the surface of conventional dendritic cells, but is constitutively expressed by a unique APC population in the intestinal lamina propria. We used two experimental IBD models to evaluate whether interfering the interaction between CD70 and its T cell ligand CD27 would affect the development of colitis. Adoptive transfer of naive CD27-deficient CD45RB(high) CD4(+) T cells into Rag-1(-/-) mice resulted in significantly less disease than when wild-type CD45RB(high)CD4(+) T cells were used. Moreover, a monoclonal anti-CD70 Ab prevented the disease caused by the transfer of wild-type CD45RB(high) CD4(+) T cells into Rag-1(-/-) mice and the same Ab also ameliorated an established disease. The colitis associated proinflammatory cytokines IL-6, TNF-alpha and IFN-gamma were significantly reduced after anti-CD70 Ab treatment, suggesting an overall reduction in inflammation due to blockade of pathogenic T cell expansion. Anti-CD70 Ab treatment also suppressed trinitrobenzene sulfonic acid-induced colitis in SJL/J mice. Because anti-CD70 Ab treatment suppressed multiple proinflammatory cytokines, this may be a more potent therapeutic approach for IBD than blockade of individual cytokines.

PMID:
19525396
[PubMed - indexed for MEDLINE]
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