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.
Highlights
IntroductionHuman anti-porcine T-cell response resembles allogenic response, in which human T cells recognize porcine major histocompatibility complex (MHC) class II antigens through the direct pathway
Xenotransplantation - the transplantation of cells, tissues or organs between individuals of different species - offers the possibility of overcoming current organ shortages, and is a potential avenue for the application of new technologies, such as, genetic engineering, cloning, and the rational design of therapeutics (Cascalho and Platt, 2001).Human anti-porcine T-cell response resembles allogenic response, in which human T cells recognize porcine major histocompatibility complex (MHC) class II antigens through the direct pathway
Xenogenic cells are known to elicit T cell responses that coincide with rejection, such as, the direct killing by CD8+ T cells of discordant xenografts
Summary
Human anti-porcine T-cell response resembles allogenic response, in which human T cells recognize porcine major histocompatibility complex (MHC) class II antigens through the direct pathway. It was recently reported that T-cell-mediated xenoimmune response is CD4+ T-cell-dependent. The activation of CD4+ T cells by immunogenic xenopeptides results in the local secretions of various cytokines, including IL-2, within xenografts. These cytokines further induce the differentiation of activated CD8+ T cells into CTLs that can kill various xenogenic and syngenic target cells in a nonspecific manner. Human CD8+ CTL clones elicit an immune response to pig antigens introduced into humans as food (Hartig et al, 2000)
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