Sequential evolution of IL-17 responses in the early period of allograft rejection.
In addition to CD4+CD25+Foxp3+ regulatory T (T(reg)) cells which protect against autoimmune tissue injury, IL-17-producing CD4+ T (T(h)17) 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 T(h)17 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 T(h)17 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 T(h)17 and T(reg) were found to gradually increase in both syngeneic and allogeneic recipients, T(h)17/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 T(h)17 and CD8+ T cells during allograft rejection. T(h)17/T(reg) imbalance is associated with the development of allograft rejection. This study would provide basic information on T(h)17 biology for future investigation in the field of transplantation.
Min
Sang Il
SI
Department of Surgery, Seoul National University College of Medicine, Seoul 110-799, Korea.
Ha
Jongwon
J
Park
Chung-Gyu
CG
Won
Jae Kyung
JK
Park
Yang Jin
YJ
Min
Seung-Kee
SK
Kim
Sang Joon
SJ
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015551:Autoimmunity; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism*; D016027:Heart Transplantation; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014181:Transplantation Immunology
D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17