Keratinocytes induce local tolerance to skin graft by activating interleukin-10-secreting T cells in the context of costimulation molecule B7-H1.

Abstract

BACKGROUND:

Intermingled skin grafting using autologous skin islets inlaid in allogeneic skin sheets was found to delay graft rejection, contributing to a significant reduction in mortality for patients with severe burns. In this study we examine the down-regulatory mechanisms underlying the effect of the autologous skin islets.

METHODS:

Mixed culture of lymphocytes with epidermal cells of autologous and allogeneic origin were performed with a comparing of cell activity from cytokine-knockout mice. And the Th1/Th2-related cytokine profiles were examined.

RESULTS:

Autologous keratinocytes act as potent inducers of suppression in the mixed culture by making a shift of the cytokine profile from Th1 to Th2. The observed suppression is predominantly mediated by interleukin (IL)-10, because the effect could be reversed by application of a neutralizing antibody to IL-10. The results of reconstitution experiments in BALB/c mice, with or without IL-10 gene-knockout, are consistent with this finding. These demonstrated that T cells were main effective components for the IL-10-related suppression. Furthermore, a newly identified member of the human B7 family (B7-H1) is found to play an important role in activating human IL-10-secreting lymphocytes. When transfected with the CD80 gene, autologous keratinocytes lost the ability to down-regulate the mixed cell culture, which effect could be reversed by introduction of the anti-CD80 antibody.

CONCLUSIONS:

Our study provides new evidence that autologous keratinocytes present in intermingled skin grafts are inducers for local immune tolerance by expression of B1-H1 in their activation of the IL-10-secreting T cells.

• Authors: Yingping Cao, Hong Zhou, Jian Tao, Zexian Zheng, Ningli Li, Baihua Shen, Tsi-Siang Shih, Jian Hong, Jingwu Zhang, Kuang-Yen Chou
• Journal: Transplantation (Transplantation) Vol. 75 Issue 8 Pg. 1390-6 (Apr 27 2003) ISSN: 0041-1337 [Print] United States
• PMID: 12717236 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• B7-1 Antigen
• B7-H1 Antigen
• Blood Proteins
• CD274 protein, human
• Cd274 protein, mouse
• Cytokines
• Membrane Glycoproteins
• Peptides
• Interleukin-10

Topics

• Animals
• Antigens, CD
• B7-1 Antigen (pharmacology, physiology)
• B7-H1 Antigen
• Blood Proteins
• Cells, Cultured
• Coculture Techniques
• Cytokines (metabolism)
• Epidermal Cells
• Epidermis (physiology)
• Humans
• Immunosuppression Therapy
• Interleukin-10 (genetics, metabolism, physiology)
• Keratinocytes (physiology)
• Lymphocyte Activation (physiology)
• Lymphocyte Culture Test, Mixed
• Membrane Glycoproteins
• Mice
• Mice, Knockout (genetics)
• Peptides
• Skin Transplantation
• T-Lymphocytes (physiology)
• Th1 Cells (metabolism)
• Th2 Cells (metabolism)
• Transplantation Tolerance