Intragraft expression of cytokine transcripts during pig proislet xenograft rejection and tolerance in mice
| Autor: | C F, Morris, C J, Simeonovic, M C, Fung, J D, Wilson, A J, Hapel |
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| Rok vydání: | 1995 |
| Předmět: |
CD4-Positive T-Lymphocytes
Graft Rejection Male DNA Complementary Base Sequence Swine Molecular Sequence Data Transplantation Heterologous Islets of Langerhans Transplantation Gene Expression Mice Fetal Tissue Transplantation Immune Tolerance Mice Inbred CBA Animals Cytokines Interleukin-2 RNA Messenger Spleen DNA Primers |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 154(5) |
| ISSN: | 0022-1767 |
| Popis: | The rejection of pig proislet (islet precursor) xenografts in CBA/H mice is a CD4+ T cell-dependent process. The molecular mechanisms of xenograft rejection, xenograft survival during anti-CD4 mAb therapy and xenograft tolerance post-withdrawal of anti-CD4 mAb administration, were examined by using a semiquantitative PCR method. Temporal analysis of intragraft cytokine mRNA demonstrated a Th0-like pattern of expression (IL-2, IFN-gamma, IL-3, IL-4, IL-5, and IL-10) on day 4 of the acute xenograft rejection process. From day 5, however, only Th2-associated transcripts (IL-3, IL-4, IL-5, and IL-10) were enhanced in xenografts compared with isograft controls. Immunohistochemistry showed that the principal participants in the rejection infiltrate were CD4+ T cells and eosinophils, with smaller numbers of CD8+ T cells. In vivo depletion of CD4+ T cells prevented xenograft rejection but had minimal effect on the peak levels of IL-2, IFN-gamma, and IL-10 mRNA; in contrast, the enhanced expression of IL-3, IL-4, and IL-5 transcripts seen in rejecting xenografts was abrogated. This established a positive correlation between acute xenograft rejection, presence of CD4+ T cells, and enhanced intragraft expression of mRNA for the Th2-type cytokines IL-3, IL-4, and IL-5. In tolerant hosts, long-term proislet xenograft survival and function (190 days) was accompanied by intragraft expression of IL-2 and IL-10 mRNA; IFN-gamma, IL-3, IL-4, and IL-5 mRNA were either undetected or not enhanced. The induced rejection of long-term functioning xenografts (170 days) in nontolerant hosts resulted in selective enhancement of IL-4 transcript expression. This study suggests that Th2-like CD4+ T cells are differentially activated in response to xenoantigen and that xenograft tolerance is associated with lack of expression of the Th2 cytokine, IL-4. |
| Databáze: | OpenAIRE |
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