CTLA-4Ig combined with ICAM-1 mAb promotes immune tolerance induced by donor-derived immature dendritic cells in recipient mice / 第二军医大学学报

ABSTRACT

Objective: To investigate the mechanism of CTIL-4Ig combined with Anti-ICAM-1 mAb in promoting immune tolerance induced by donor-derived immature dendritic cells (imDC) in recipient mice. Methods: Male mice were divided into 4 groups control group (receiving only imDC), CTLA-4Ig group, ICAM-1 mAb group and CTLA-4Ig + ICAM-1 group. Mice were transfused with donor-derived imDC 7 days before they received heart transplantation in company with daily injection of ICAM-1 mAb, CTLA-4Ig or both for the following 2 weeks. Immunological analysis was performed in mice 7 days and 21 days after heart transplantation. Results: CTLA-4Ig alone or in combination with ICAM-1 mAb significantly inhibited T cells proliferation to alloantigen stimulation, impaired lymphocyte cytotoxicity, suppressed production of IL-2, IFN-γ by Th1, increased production of IL-10, and obviously decreased the production of alloantibody IgG in recipient mice treated with donor-derived imDC. ICAM-1 mAb alone had no significant effects on T cells proliferation and production of Th-derived cytokines except for IL-2. Conclusion: ICAM-1 mAb combined with CTLA-4Ig can enhance immune tolerance induced by donor-derived imDC in recipient mice through induction of T cells hypo-responsiveness, inhibition of lymphocyte cytotoxicity and B cell immunoreation, and promotion of Th2 polarization in vivo.