αcD2 mAb treatment safely attenuates adoptive transfer colitis

Abstract

Increased proliferation, defective apoptosis, and cytokine dysregulation of T lymphocytes are thought to be important for the pathogenesis of inflammatory bowel disease. Since these phenomena can be corrected by αCD2 mAb, we asked whether CD2 directed immunotherapy safely prevents and/or ameliorates adoptive transfer colitis. Colitis was induced by transfer of CD4+ T cell blasts to syngenic RAG1-/- mice or CD45RBhigh CD4+ T cells to SCID mice. The αCD2 mAb 12-15 or rat IgG was given, starting either initially or upon first signs of colitis. Disease activity was assessed by clinical monitoring, microscopic scoring, hemoccult, endoscopy, and blood count analysis. Cytokine production of stimulated LPL was measured by ELISA and cell proliferation by [3H]-thymidine incorporation. Parasite control was analyzed in a murine model of infection with Toxoplasma gondii. The αCD2 mAb significantly increased mean survival time when starting at transfer of blasts (survival > 35 days: αCD2 69% vs 0% of controls, P <0.05). In the preventive experiment the αCD2 mAb markedly reduced IL-2 secretion and T-cell proliferation. The immune response towards Toxoplasma gondii was not impaired. These studies show for the first time that CD2 directed immunotherapy can attenuate or delay adoptive transfer colitis and ameliorate established colitis. Most likely inhibition of IL-2 secretion and T-cell proliferation are responsible for these effects. Still, immune defence towards T. gondii is maintained. © 2005 USCAP, Inc All rights reserved.