An Immunoadhesin Incorporating the Molecule OX-2 Is a Potent Immunosuppressant That Prolongs Allo- and Xenograft Survival
| Autor: | R M, Gorczynski, M S, Cattral, Z, Chen, J, Hu, J, Lei, W P, Min, G, Yu, J, Ni |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Recombinant Fusion Proteins Transplantation Heterologous Immunology Mice Nude Antibodies Heterophile Lymphocyte Activation Mice Antigens CD Immune Tolerance Animals Transplantation Homologous Immunology and Allergy Infusions Intravenous Cells Cultured Mice Inbred BALB C Mice Inbred C3H Membrane Glycoproteins Sheep Immune Sera Graft Survival Antibodies Monoclonal Kidney Transplantation Growth Inhibitors Immunoglobulin Fc Fragments Rats Mice Inbred C57BL Kinetics Rats Inbred Lew Antigens Surface B7-1 Antigen Cytokines B7-2 Antigen Lymphocyte Culture Test Mixed Cell Adhesion Molecules Immunosuppressive Agents T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Immunology. 163:1654-1660 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.163.3.1654 |
| Popis: | We have established that, in mice receiving donor-specific immunization by the portal vein, the increased graft survival seen is associated with the increased expression of a molecule (OX-2) on a subpopulation of dendritic cells (DC), and polarization of cytokine production to type 2 cytokines on Ag-specific restimulation of cells from these mice. Furthermore, infusion of a mAb to OX-2 blocks both the increased graft survival and the altered cytokine production seen. We have constructed an immunoadhesin in which the extracellular domain of OX-2 is linked to the murine IgG2a Fc region, and we have expressed this molecule (OX-2:Fc) in a eukaryotic (baculovirus) expression system. Incubation of lymphocytes with 50 ng/ml OX-2:Fc inhibits a primary mixed lymphocyte reaction in vitro, as assayed by proliferation and induction of cytotoxic T cells, and also alters cytokine production with decreased IL-2 (IFN-γ) production and increased IL-4 (IL-10) production. Similarly, in vivo infusion of OX-2:Fc promotes increased allo- and xenograft (both skin and renal grafts) survival and decreases the Ab response to sheep erythrocytes. Our data suggest this molecule might have clinical importance in allo- and xenotransplantation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|