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

다국어 초록 (Multilingual Abstract)

In addition to CD4+CD25+Foxp3+ regulatory T (Treg) 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 Treg 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 Treg 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 Treg were found to gradually increase in both syngeneic and allogeneic recipients, Th17/Treg 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/Treg 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.

참고문헌 (Reference)

1 Niimi M, "The technique for heterotopic cardiac transplantation in mice: experience of 3000 operations by one surgeon" 20 : 1123-1128, 2001

2 Cheng X, "The Th17/Treg imbalance in patients with acute coronary syndrome" 127 : 89-97, 2008

3 Amadi-Obi A, "Th17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1" 13 : 711-718, 2007

4 Mosmann TR, "Th1 and Th2 cells: different patterns of lymphokine secretion lead to different functional properties" 7 : 145-173, 1989

5 Tan CD, "Rodriguez ER. Update on cardiac transplantation pathology" 131 : 1169-1191, 2007

6 Stewart S, "Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection" 24 : 1710-1720, 2005

7 Bettelli E, "Reciprocal developmental pathways for the generation of pathogenic effector Th17 and regulatory T cells" 441 : 235-238, 2006

8 Mucida D, "Reciprocal Th17 and regulatory T cell differentiation mediated by retinoic acid" 317 : 256-260, 2007

9 Corry RJ, "Primarily vascularized allografts of hearts in mice. The role of H-2D, H-2K, and non-H-2 antigens in rejection" 16 : 343-350, 1973

10 Hoshino A, "MPO-ANCA induces IL-17 production by activated neutrophils in vitro via classical complement pathway-dependent manner" 31 : 79-89, 2008

11 Cua DJ, "Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain" 421 : 744-748, 2003

12 Aggarwal S, "Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17" 278 : 1910-1914, 2003

13 Zheng Y, "Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis" 445 : 648-651, 2007

14 Tzartos JS, "Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis" 172 : 146-155, 2008

15 Tang JL, "Interleukin-17 antagonism inhibits acute but not chronic vascular rejection" 72 : 348-350, 2001

16 Van Kooten C, "Interleukin-17 activates human renal epithelial cells in vitro and is expressed during renal allograft rejection" 9 : 1526-1534, 1998

17 Fujino S, "Increased expression of interleukin 17 in inflammatory bowel disease" 52 : 65-70, 2003

18 Chan SY, "In vivo depletion of CD8+ T cells results in Th2 cytokine production and alternate mechanisms of allograft rejection" 59 : 1155-1161, 1995

19 Bishop DK, "Immunobiology of allograft rejection in the absence of IFN-gamma: CD8+ effector cells develop independently of CD4+ cells and CD40-CD40 ligand interactions" 166 : 3248-3255, 2001

20 Langrish CL, "IL-23 drives a pathogenic T cell population that induces autoimmune inflammation" 201 : 233-240, 2005

21 Korn T, "IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells" 448 : 484-487, 2007

22 Benghiat FS, "IL-17 production elicited by allo-major histocompatibility complex class II recognition depends on CD25posCD4pos T cells" 85 : 943-949, 2008

23 Mi-La Cho, "IL-17 induces the production of IL-16 in rheumatoid arthritis" 생화학분자생물학회 40 (40): 237-245, 2008

24 Kotake S, "IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis" 103 : 1345-1352, 1999

25 Weaver CT, "IL-17 family cytokines and the expanding diversity of effector T cell lineages" 25 : 821-852, 2007

26 Hsieh HG, "IL-17 expression as a possible predictive parameter for subclinical renal allograft rejection" 14 : 287-298, 2001

27 Dieckmann D, "Human CD4(+)CD25(+) regulatory, contact-dependent T cells induce interleukin 10-producing, contact-independent type 1-like regulatory T cells [corrected]" 196 : 247-253, 2002

28 Ng WF, "Human CD4(+)CD25(+) cells: a naturally occurring population of regulatory T cells" 98 : 2736-2744, 2001

29 Fyfe B, "Heart transplantation-associated perioperative ischemic myocardial injury. Morphological features and clinical significance" 93 : 1133-1140, 1996

30 Li J, "Gene transfer of soluble interleukin-17 receptor prolongs cardiac allograft survival in a rat model" 29 : 779-783, 2006

31 Abbas AK, "Functional diversity of helper T lymphocytes" 383 : 787-793, 1996

32 Sakaguchi S, "Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease" 212 : 8-27, 2006

33 Fontenot JD, "Foxp3 programs the development and function of CD4+CD25+ regulatory T cells" 4 : 330-336, 2003

34 Loong CC, "Evidence for the early involvement of interleukin 17 in human and experimental renal allograft rejection" 197 : 322-332, 2002

35 Martinez OM, "Evidence for a nonclassical pathway of graft rejection involving interleukin 5 and eosinophils" 55 : 909-918, 1993

36 Xu L, "Cutting edge: regulatory T cells induce CD4+CD25-Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-beta" 178 : 6725-6729, 2007

37 Kryczek I, "Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment" 178 : 6730-6733, 2007

38 Burrell BE, "CD8+ Th17 mediate costimulation blockade-resistant allograft rejection in T-bet-deficient mice" 181 : 3906-3914, 2008

39 Homey B, "After Th1/Th2 now comes Treg/Th17: significance of T helper cells in immune response organization]" 57 : 730-732, 2006

40 Yuan X, "A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy" 205 : 3133-3144, 2008