Exp Mol Med.  2006 Oct;38(5):574-582.

Immunosuppression of xenograft rejection in porcine kidney PK15 cells by porcine IL-18

• Choi YS
• Kim YK
• Shim JH
• Kim EM
• Kang HS
• Yoon DY
• Muneta Y
• Myung PK

Abstract

Xenotransplantation, the transplantation of cells, tissues or organs between individuals of different species, would resolve the current shortage of organs, but rejection remains the major hurdle to successful xenotransplantation. In the present study, we analyzed mixed lymphocyte reactions (MLRs) and used 51Cr release assays in order to identify the proliferation and expansion of mouse CD8+ cytotoxic T lymphocyte cells against PK15, PK15/pIL-18 or PK15/mIL-18 cells. In addition, we identified T cell populations in mouse splenocytes and lymph node cells using two-color flow cytometry. It was found that the CD8+T cells of xenograft recipients proliferated extensively and that the survival rates of populations of PK15/mIL-18 or PK15/pIL-18 cells were higher than untransfected controls. Moreover, CD3+T cells were increased in mice injected with PK15 cells or PK15/pIL-18 cells but PK15/pIL-18 cell numbers were lower in lymph nodes than untransfected controls. CD8+T cells numbers were reduced in the lymph nodes of PK15/pIL-18 injected mice. These results suggest that porcine IL-18 regulates anti-pig cellular rejection in C57BL/6 mice.

Keyword

CD8-positive T lymphocytes; graft rejection; interleukin-18; kidney; pig

MeSH Terms

Transplantation, Heterologous
Transplantation
Transgenes/immunology/physiology
Transfection
Tissue Distribution
T-Lymphocytes/metabolism
Swine
RNA, Messenger/metabolism
Phenotype
Mice, Inbred C57BL
Mice
Lymphocyte Culture Test, Mixed
Lymphocyte Activation
Kidney/cytology/*immunology
Interleukin-18/*genetics/metabolism/physiology
Immunosuppression/*methods
Graft Rejection/immunology/*prevention & control
Genetic Vectors/chemical synthesis
Female
Epithelial Cells/*drug effects/*transplantation
Cytokines/metabolism
Cells, Cultured
Animals