A comparison of corneal, pancreas, and skin grafts in mice. A study of the determinants of tissue immunogenicity.
A model of murine heterotopic allogeneic transplantation was used to study the rejection characteristics of three tissues--adult cornea, fetal pancreas, and fetal skin--for attributes that might explain their variation in rejection rates and help define the determinants of graft immunogenicity. Under identical conditions, tissues were transplanted to the renal subcapsular space and their base-line rejection rates compared. The expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1), was determined for each tissue, as was their ability to produce interleukin-6, IL-3, interferon-gamma, and granulocyte-macrophage colony-stimulating factor in vitro. These studies were performed under basal conditions and after stimulation with concanavalin A-stimulated spleen cell supernatant (CAS) or INF gamma. Corneal grafts had a slow rejection rate compared with pancreas and skin. While all three tissues had low basal expression of MHC class II, both fetal skin and pancreas, but not adult cornea, were able to increase this under our experimental conditions. Pancreas and skin produced IL-6 under basal conditions and could be stimulated to increase production 2-3-fold but the cornea did not basally produce IL-6 and showed minimal upregulation. We postulate that delayed corneal rejection, compared with pancreas and skin, results from two compounding deficiencies: the relative lack of class II MHC-positive APC and the inability to overcome this deficiency by upregulating class II expression and producing accessory molecules for antigen presentation.
Guymer
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RH
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Mandel
T E
TE
D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology; D003315:Cornea / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D016039:Corneal Transplantation / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes; D016332:Fetal Tissue Transplantation / Q000276:immunology; D006084:Graft Rejection; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000187:drug effects / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D007668:Kidney; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010179:Pancreas / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D016035:Pancreas Transplantation / Q000276:immunology*; D012867:Skin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D016038:Skin Transplantation / Q000276:immunology*; D016042:Transplantation, Heterotopic
D015815:Cell Adhesion Molecules; D016207:Cytokines; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor