Development of a novel transgenic mouse for the study of interactions between CD4 and CD8 T cells during graft rejection.
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.
Ehst
Benjamin D
BD
Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, USA.
Ingulli
Elizabeth
E
Jenkins
Marc K
MK
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002645:Chickens; D006085:Graft Survival; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010047:Ovalbumin / Q000096:biosynthesis / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000378:metabolism; D018800:Thy-1 Antigens / Q000096:biosynthesis; D013997:Time Factors; D019076:Transgenes
D008024:Ligands; D018800:Thy-1 Antigens; D010047:Ovalbumin; D017493:Leukocyte Common Antigens