Alloprimed CD8+ T cells Regulate Alloantibody and Eliminate Alloprimed B cells through Perforin- and FasL-dependent mechanisms
| Autor: | K. J. Tobin, S. M. Elzein, P. B. Sanghavi, C. L. Wright, T. A. Pham, Ginny L. Bumgardner, V. M. Sanders, Jason M. Zimmerer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Fas Ligand Protein
Blotting Western chemical and pharmacologic phenomena Mice Transgenic CD8-Positive T-Lymphocytes Immunoglobulin G Article Interleukin 21 Mice Isoantibodies MHC class I Immunology and Allergy Cytotoxic T cell Animals Transplantation Homologous Pharmacology (medical) Cells Cultured Mice Knockout Transplantation B-Lymphocytes biology Perforin Tumor Necrosis Factor-alpha hemic and immune systems Flow Cytometry Liver Transplantation Mice Inbred C57BL Immunology Antibody Formation biology.protein Hepatocytes Tumor necrosis factor alpha CD8 |
| Popis: | While it is well known that CD4(+) T cells and B cells collaborate for antibody production, our group previously reported that CD8(+) T cells down-regulate alloantibody responses following transplantation. However, the exact mechanism involved in CD8(+) T cell-mediated down-regulation of alloantibody remains unclear. We also reported that alloantibody production is enhanced when either perforin or FasL is deficient in transplant recipients. Here, we report that CD8(+) T cell-deficient transplant recipient mice (high alloantibody producers) exhibit an increased number of primed B cells compared to WT transplant recipients. Furthermore, CD8(+) T cells require FasL, perforin and allospecificity to down-regulate posttransplant alloantibody production. In vivo CD8-mediated clearance of alloprimed B cells was also FasL- and perforin-dependent. In vitro data demonstrated that recipient CD8(+) T cells directly induce apoptosis of alloprimed IgG1(+) B cells in co-culture in an allospecific and MHC class I-dependent fashion. Altogether these data are consistent with the interpretation that CD8(+) T cells down-regulate posttransplant alloantibody production by FasL- and perforin-dependent direct elimination of alloprimed IgG1(+) B cells. |
| Databáze: | OpenAIRE |
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