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Development of a Novel Transgenic Mouse for the Study of Interactions Between CD4 and CD8 T Cells During Graft Rejection
Author(s) -
Ehst Benjamin D.,
Ingulli Elizabeth,
Jenkins Marc K.
Publication year - 2003
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1046/j.1600-6135.2003.00246.x
Subject(s) - cd8 , cytotoxic t cell , major histocompatibility complex , antigen , ovalbumin , immunology , biology , microbiology and biotechnology , in vitro , biochemistry
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 wild‐type 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 .