Antigen-Specific Cytotoxic T Cells Mediate Human Fetal Pancreas Allograft Rejection in SCID-hu Mice

Matthieu Rouleau, Reiko Namikawa, Svetlana Antonenko, Nicole Carballido-Perrig, Maria Grazia Roncarolo

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Abstract

Human allograft rejection was studied in SCID mice transplanted with human fetal liver and thymus tissue (SCID-hu mice). These SCID-hu mice have functional, mature T cells with a polyclonal TCR repertoire. Within 12 to 36 wk after construction, SCID-hu mice were transplanted with an HLA-mismatched human fetal pancreas. In contrast to control SCID mice transplanted with pancreas alone, cellular infiltration, induction of HLA-DR on pancreatic epithelial cells, and tissue destruction of the allogenic pancreata were observed in SCID-hu mice. In addition, human insulin was not detected in the serum of SCID-hu mice in which pancreas rejection occurred. The infiltrating cells were mainly human CD3+ T lymphocytes of thymic origin, expressing the CD45RO isoform. T cell lines and CD4+ T cell clones obtained from the rejected tissues proliferated vigorously when stimulated with EBV-transformed B cell lines of pancreas donor origin. Furthermore, the majority of these CD4+ T cell clones displayed strong allospecific cytotoxicity. In addition, CD8+ T cell clones cytotoxic for EBV-transformed B cell lines of pancreas donors were isolated. Blocking experiments with anti-HLA mAbs and panel studies with HLA-matched cell lines showed that these CD4+ and CD8+ T cell clones were specific for the HLA class II and class I molecules, respectively, expressed by the pancreas donor. These data indicate that human T lymphocytes developing in SCID-hu mice are able to mount in vivo responses against allogenic organs, resulting in tissue infiltration and rejection. In addition, they show that both CD4+- and CD8+-allospecific CTL can be isolated from rejected allogenic pancreata.

Original languageEnglish
Pages (from-to)5710-5720
Number of pages11
JournalJournal of Immunology
Volume157
Issue number12
Publication statusPublished - Dec 15 1996

ASJC Scopus subject areas

  • Immunology

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    Rouleau, M., Namikawa, R., Antonenko, S., Carballido-Perrig, N., & Roncarolo, M. G. (1996). Antigen-Specific Cytotoxic T Cells Mediate Human Fetal Pancreas Allograft Rejection in SCID-hu Mice. Journal of Immunology, 157(12), 5710-5720.