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PROLONGATION OF SKIN ALLOGRAFT SURVIVAL IS ASSOCIATED WITH REDUCED Th1 CYTOKINE RESPONSES IN THE WKY???F344 RAT MODEL
- Source :
- Transplantation. 68:1393-1401
- Publication Year :
- 1999
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 1999.
-
Abstract
- BACKGROUND We have reported previously that F344 rats develop a spontaneous tolerance to WKY lung allografts and show long-term retention of donor-specific skin grafts placed 35 days after lung transplantation. In this study, we investigated the immunologic mechanisms that may be responsible for the prolonged skin graft survival in animals tolerized with lung allografts. METHODS In the rejection group, WKY skin grafts were placed on normal F344 rats, whereas, in the tolerance group, the skin grafts were placed on F344 rats that had received a WKY lung transplant 35 days before skin grafting. Th1 (interleukin [IL]-2 and interferon-gamma [IFN-gamma]) and Th2 (IL-4 and IL-10) cytokine as well as transforming growth factor-beta1 mRNA expression in skin grafts and in draining lymph nodes were determined by reverse transcription-polymerase chain reaction. Macrophage and lymphocyte infiltration in skin grafts and the number of Langerhans cells in epidermal sheets of the grafts were examined by immunohistochemistry. RESULTS IL-2 and IFN-gamma mRNA expression was significantly decreased in both the skin grafts and the draining lymph nodes of the tolerance group, compared to the rejection group, whereas IL-10 and transforming growth factor-beta1 mRNA expression was similar in both groups and IL-4 mRNA was rarely detected. Decreased and delayed CD8+, macrophage, and natural killer cell infiltration in the skin grafts from the tolerance group was also detected. Similar reduction in the number of Langerhans cells in the epidermis of the grafts from both groups was seen on day 1 after skin grafting, and thereafter the number remained stable in both groups. CONCLUSIONS Reduced expression of Th1 cytokines and decreased infiltration of CD8+ cells, macrophages, and natural killer cells in the skin grafts may be responsible for prolongation of skin graft survival in the tolerance group.
- Subjects :
- Graft Rejection
Male
Pathology
medicine.medical_specialty
medicine.medical_treatment
Rats, Inbred WKY
Natural killer cell
Immune tolerance
Th2 Cells
Immune system
Transforming Growth Factor beta
medicine
Animals
Transplantation, Homologous
RNA, Messenger
Transplantation
integumentary system
business.industry
Graft Survival
Interleukin
Skin Transplantation
Th1 Cells
Rats, Inbred F344
Rats
surgical procedures, operative
Cytokine
medicine.anatomical_structure
Immunology
Cytokines
Skin grafting
Lymph
business
Lung Transplantation
Subjects
Details
- ISSN :
- 00411337
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- Transplantation
- Accession number :
- edsair.doi.dedup.....7820f5e8fec89137a41079fbe1827b99