Search results for: Hamster Anti-Mouse CD28 Antibodies
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Costimulation blockade of CD40 and CD28 pathways in limb transplantation.
Costimulation blockade remains a promising experimental regimen for the induction of transplantation tolerance. The simultaneous blockade of both the CD40 and CD28 pathways has been synergistic in prolonging organ allograft survival but has not previously been investigated in a model of limb allotransplantation. This study determined the efficacy of this combination in the murine limb allograft model. C57B1/6 (H-2K(b)) female mice were recipients of heterotopic vascularized limb allografts from Balb/c (H-2K(d)) male donors. Experimental groups received treatment with a short course of MR1 (hamster anti-mouse anti-CD40 ligand antibody) alone or in combination with CTLA4-Ig, a fusion protein that blocks the B7/CD28 pathway. Untreated recipients rejected limb allografts at a mean of 9.6 +/- 1.1 (standard error of the mean) days postoperatively. Recipients of a prolonged course of MR1 rejected limb allografts at 75 +/- 25 days. When both MR1 and CTLA4-Ig were used, limb allograft survival of >120 days was observed despite a much shorter course of therapy. Rejection in both treatment groups was consistent with a chronic antibody-mediated process. Donor antigen rechallenge in these recipients by in vitro assay and skin allograft demonstrated a hyperacute response consistent with presensitization. Long-term limb allograft survival is produced by the synergistic effect of blocking both the CD40 and CD28 costimulatory pathways. However, permanent acceptance was not achieved, and allografts eventually succumbed to what appeared to be antibody-mediated rejection. The additional use of newer agents that block more recently described costimulatory pathways may be essential for the induction of tolerance by costimulation blockade.T H H Tung, S E Mackinnon, T Mohanakumar
1209 related Products with: Costimulation blockade of CD40 and CD28 pathways in limb transplantation.
5mg100 μg100μg100 μg100ug Lyophilized200ul1,000 tests 100ul96 assays
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Expression of programmed death 1 ligands by murine T cells and APC.
Programmed death 1 (PD-1) is a new member of the CD28/CTLA-4 family, which has been implicated in the maintenance of peripheral tolerance. Two ligands for PD-1, namely, B7-H1 (PD-L1) and B7-DC (PD-L2), have recently been identified as new members of the B7 family but their expression at the protein level remains largely unknown. To characterize the expression of B7-H1 and B7-DC, we newly generated an anti-mouse B7-H1 mAb (MIH6) and an anti-mouse B7-DC mAb (TY25). MIH6 and TY25 immunoprecipitated a single molecule of 43 and 42 kDa from the lysate of B7-H1 and B7-DC transfectants, respectively. Flow cytometric analysis revealed that B7-H1 was broadly expressed on the surface of mouse tumor cell lines while the expression of B7-DC was rather restricted. PD-1 was expressed on anti-CD3-stimulated T cells and anti-IgM plus anti-CD40-stimulated B cells at high levels but was undetectable on activated macrophages or DCs. B7-H1 was constitutively expressed on freshly isolated splenic T cells, B cells, macrophages, and dendritic cells (DCs), and up-regulated on T cells by anti-CD3 stimulation on macrophages by LPS, IFN-gamma, GM-CSF, or IL-4, and on DCs by IFN-gamma, GM-CSF, or IL-4. In contrast, B7-DC expression was only inducible on macrophages and DCs upon stimulation with IFN-gamma, GM-CSF, or IL-4. The inducible expression of PD-1 ligands on both T cells and APCs may suggest new paradigms of PD-1-mediated immune regulation.Tomohide Yamazaki, Hisaya Akiba, Hideyuki Iwai, Hironori Matsuda, Mami Aoki, Yuka Tanno, Tahiro Shin, Haruo Tsuchiya, Drew M Pardoll, Ko Okumura, Miyuki Azuma, Hideo Yagita