Regulation of B- and T-cell mediated xenogeneic transplant rejection by interleukin 12
| Autor: | Hao Wang, Jifu Jiang, Mark E. DeVries, Karoline A. Hosiawa, Robert Zhong, Bertha Garcia, Dejun Zhou, Mark J. Cameron, David J. Kelvin |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
CD4-Positive T-Lymphocytes
Graft Rejection DNA Complementary Xenotransplantation medicine.medical_treatment T cell Transplantation Heterologous Antibodies Heterophile Lymphocyte Activation Immune tolerance Mice medicine Immune Tolerance Animals Humans Transplantation Homologous B cell Heart transplantation Mice Knockout Transplantation B-Lymphocytes Mice Inbred C3H biology Base Sequence business.industry Interleukin-12 Subunit p40 medicine.disease Interleukin-12 Transplant rejection Rats Mice Inbred C57BL Protein Subunits medicine.anatomical_structure Granzyme Rats Inbred Lew Immunology biology.protein Heart Transplantation business |
| Zdroj: | Transplantation. 81(2) |
| ISSN: | 0041-1337 |
| Popis: | Background. Xenotransplantation may provide a solution to the increasing shortage of donor organs. Acute vascular rejection and cell-mediated rejection remain the primary barriers to successful xenotransplantation. In animal models where acute vascular rejection can be attenuated, xenografts succumb to cell-mediated rejection. The mechanisms of acute vascular rejection and cell-mediated rejection are poorly understood. Methods. Using a heterotopic rat-to-mouse cardiac transplantation model, we demonstrate that IL-12p40 attenuates both allogeneic and xenogeneic acute vascular rejection pathology by suppressing B-cell activation and anti-rat isotype switching. To study the mechanism of xenogeneic cell-mediated rejection, we use B-cell deficient mice that only develop cell-mediated rejection pathology. To elucidate the role of IL-12 in cell-mediated rejection, we generated B cell/ IL-12p40 double knockout mice. Results. We demonstrate that xenogeneic cell-mediated rejection is mediated by CD4 + T cells, and is accompanied by elevated FasL and granzyme mRNA expression. Strikingly, by generating B cell/IL-12p40 double knockout mice, we demonstrate that xenogeneic cell-mediated rejection is IL-12p40 dependent. In contrast, we demonstrate that allogeneic cellular rejection is IL-12p40 independent. Conclusions. We conclude that IL-12 plays a dual role in xenotransplantation by driving xenogeneic CD4 + T cell responses but suppressing both allogeneic and xenogeneic B cell responses. Therefore, the mechanism of allogeneic and xenogeneic transplantation rejection is differentially regulated by IL-12. |
| Databáze: | OpenAIRE |
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