Development of a Novel Transgenic Mouse for the Study of Interactions Between CD4 and CD8 T Cells During Graft Rejection

Benjamin D. Ehst, Elizabeth Ingulli, Marc K. Jenkins

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

The goal of this study was the development of a system in which the cooperative interactions between CD4 and CD8 T cells specific for defined peptides from a single minor histocompatibility antigen could be studied. A transgenic mouse strain that expresses chicken ovalbumin (Act-mOVA) on the surface of all cells in the body was produced as a source of tissues containing such an antigen. Skin grafts from Act-mOVA donors were rapidly and completely rejected by wildtype recipients, but only when both CD4 and CD8 T cells were present. CD4 T cells by themselves caused an incomplete form of rejection characterized by rapid but partial contraction of Act-mOVA grafts. CD8 T cells alone caused complete rejection of Act-mOVA skin grafts but only after a long delay. Adoptively transferred ovalbumin-specific TCR-transgenic CD4 and CD8 T cells were stimulated by Act-mOVA graft antigens and CD8 T-cell accumulation in the grafts was enhanced by specific CD4 T cells. These findings, together with the fact that the ligand for ovalbumin peptide-specific CD8 T cells can be detected in Act-mOVA tissues with an MHC-restricted antibody, make this an ideal system for the study of cooperation between CD4 and CD8 T cells.

Original languageEnglish (US)
Pages (from-to)1355-1362
Number of pages8
JournalAmerican Journal of Transplantation
Volume3
Issue number11
DOIs
StatePublished - Nov 1 2003

Keywords

  • Adoptive transfer
  • Ovalbumin
  • Skin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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