Renal allograft rejection: examination of delayed differentiation of Treg and Th17 effector T cells.
Antigen presentation after kidney transplantation occurs in lymphoid tissues remote from the allograft, with activated T cells then migrating towards the graft. This study examined the possibility that these activated T cells can differentiate to acquire Th17 or Treg phenotypes after a time consistent with their arrival within renal allograft tissues. An immunocytochemical study was performed to demonstrate the response to intragraft TGF-β and the phenotype of lymphoid cells within rejecting human renal allograft tissue. A series of in vitro experiments was then performed to determine the potential to induce these phenotypes by addition of appropriate cytokines 3days after initial T cell activation. During renal allograft rejection there was a strong response to TGF-β, and both FOXP3 and IL-17A were expressed by separate lymphoid cells in the graft infiltrate. FOXP3 could be induced to high levels by the addition of TGF-β1 3days after the initiation of allogeneic mixed leukocyte culture. This Treg marker was enriched in the sub-population of T cells expressing the cell-surface αE(CD103)β7 integrin. The RORγt transcription factor and IL-17A were induced 3days after T cell activation by the addition of TGF-β1, IL-1β, IL-6 and IL-23; many of these Th17 cells also co-expressed CD103. T cells can develop an effector phenotype following cytokine stimulation 3days after initial activation. This suggests that the intragraft T cell phenotype may be indicative of the prevailing cytokine microenvironment.
Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
Marcin
M
Pekalski
Sarah E
SE
Jenkinson
Joseph D P
JD
Willet
Elizabeth F M
EF
Poyner
Abdulaziz H
AH
Alhamidi
Helen
H
Robertson
Simi
S
Ali
John A
JA
Kirby
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D016207:Cytokines / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism; D016030:Kidney Transplantation / Q000379:methods*; D007959:Lymphocyte Culture Test, Mixed; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014184:Transplantation, Homologous
D015703:Antigens, CD; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D039001:Integrin alpha Chains; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539901:Rorc protein, mouse; C091367:alpha E integrins