T helper17 cells are sufficient but not necessary to induce acute graft-versus-host disease.
T helper (Th)1 cells were considered responsible for the induction of graft-versus-host disease (GVHD), but recently the concept has been challenged. Th17 cells play a critical role in mediating autoimmune diseases, but their role in the pathogenesis of GVHD remains unclear. Herein we compare the ability of in vitro generated Th1 and Th17 cells from C57BL/6 mice to induce GVHD in lethally irradiated BALB/c recipients. Allogeneic Th17 cells had superior expansion and infiltration capabilities in GVHD target organs, which correlated with their increased pathogenicity when compared with naïve or Th1 controls. Th17 cells caused no pathology in the syngeneic recipients, indicating that antigen-activation was required for their pathogenicity. Polarized Th17 cells could not maintain their phenotype in vivo as they produced a significant amount of interferon (IFN)-gamma after being transplanted into allogeneic recipients; however, IFN-gamma was not required for Th17 cell-induced GVHD. Further, we evaluated the pathogenesis of Th17 cells in GVHD by using polyclonal nonprimed CD4T cells in a clinically relevant allogeneic bone marrow transplantation (BMT) setting. We found that disruption of Th17-differentiation alone by targeting RORgammat (Th17-specific transcription factor) had no significant effect on GVHD development. We conclude that Th17 cells are sufficient but not necessary to induce GVHD.
Iclozan
Cristina
C
Immunology and Blood & Marrow Transplantation Programs, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33512, USA.
Yu
Yu
Y
Liu
Chen
C
Liang
Yaming
Y
Yi
Tangsheng
T
Anasetti
Claudio
C
Yu
Xue-Zhong
XZ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000473:pathology; D017252:CD3 Complex / Q000502:physiology; D002478:Cells, Cultured; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006087:Graft vs Host Reaction / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000172:deficiency / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000172:deficiency; D012720:Severity of Illness Index; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology / Q000637:transplantation; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051598:Whole Body Imaging
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma