Exp Mol Med.  2009 Oct;41(10):707-716. 10.3858/emm.2009.41.10.077.

Sequential evolution of IL-17 responses in the early period of allograft rejection

• Min SI
• Ha J
• Park CG
• Won JK
• Park YJ
• Min SK
• Kim SJ

• KMID: 1009392
• DOI: http://doi.org/10.3858/emm.2009.41.10.077

Abstract

In addition to CD4+CD25+Foxp3+ regulatory T (T(reg)) cells which protect against autoimmune tissue injury, IL-17-producing CD4+ T (Th17) cells have been recently described and shown to play a crucial role in autoimmune injury. It appears that there is a reciprocal developmental pathway between Th17 and T(reg) cells. Although IL-17 is known to be associated with allograft rejection, the cellular source of IL-17 and the nature of Th17 in the context of allograft rejection remain unknown. In the current study, the dynamics of T(reg) and IL-17-producing cells after syngeneic and allogeneic transplantation were examined using a wild-type murine cardiac transplantation model. Ly6G+ cells were found to produce IL-17 during the early postoperative period and CD8+ as well as CD4+ T cells were also found to produce IL-17 during alloimmune response. Graft-infiltrating Ly6G+, CD4+, and even CD8+ cells were found to express IL-17 highly compared to those in spleen. Although the frequencies of Th17 and T(reg) were found to gradually increase in both syngeneic and allogeneic recipients, Th17/T(reg) ratios were significantly higher in recipients with allograft rejection than in syngeneic recipients. In conclusion, IL-17 is produced by neutrophils during the early postoperative period and subsequently by Th17 and CD8+ T cells during allograft rejection. Th17/T(reg) imbalance is associated with the development of allograft rejection. This study would provide basic information on Th17 biology for future investigation in the field of transplantation.

Keyword

graft rejection; interleukin-17; neutrophils; T-lymphocytes, regulatory

MeSH Terms

Animals
Antigens, CD/biosynthesis
Autoimmunity
Forkhead Transcription Factors/biosynthesis
Graft Rejection/immunology/*metabolism
Heart Transplantation
Interleukin-17/immunology/*secretion
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neutrophils/immunology/*metabolism/pathology
T-Lymphocyte Subsets/immunology/*metabolism
T-Lymphocytes, Regulatory/immunology/*metabolism
Time Factors
Transplantation Immunology