Adoptive transfer of CTLA4-Ig-modulated dendritic cells improves TNBS-induced colitis

Abstract

AbstractDendritic cells (DCs) play a crucial role in balancing immune responses, and in that sense the interactions between the B7-1 and B7-2 molecules expressed on DCs and CD28 and CTLA-4 on helper T cells are fundamental. While coupling of B7 and CD28 molecules activates immune responses, binding of B7 to CTLA4 results in its blockade. CTLA4-Ig fusion protein, a competitor molecule of the B7-CD28 interaction, has been used for the development of immunological tolerance both experimentally and in patients. Here, we evaluated the effects of adoptive transfer of bone marrow-derived dendritic cells (BMDCs) pulsed with CTLA4-Ig in TNBS-induced colitis. CTLA4-Ig-modulated BMDCs or naïve BMDC were administered intravenously to BALB/c mice prior to TNBS rectal instillation. Five days later, spleens and colon segments were removed for immunological and histological analysis. Our results showed that the adoptive transfer of CTLA4-Ig-modulated BMDCs was able to reduce the severity of inflammation caused by the administration of TNBS, in view of tissue integrity and reduced leukocyte infiltration in the colon segments of the treated mice compared to controls. Non-specific spleen cell activation in vitro showed a reduction in the frequency of CD4+ IL-17+ T cells and CD4+ IFN-γ+ T cells as well as IL-9 secretion in cultures. To our knowledge, this is the first description of the beneficial effects of treatment with CTLA4-Ig modulated BMDC in experimental colitis.