Faculty Collaboration Database

T helper17 cells are sufficient but not necessary to induce acute graft-versus-host disease. Biol Blood Marrow Transplant 2010 Feb;16(2):170-8

Date

10/07/2009

Pubmed ID

19804837

Pubmed Central ID

PMC3876952

DOI

10.1016/j.bbmt.2009.09.023

Scopus ID

2-s2.0-75149118145 (requires institutional sign-in at Scopus site)   88 Citations

Abstract

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.

Author List

Iclozan C, Yu Y, Liu C, Liang Y, Yi T, Anasetti C, Yu XZ

Author

Xue-Zhong Yu MD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Monoclonal
Body Weight
Bone Marrow Transplantation
CD3 Complex
Cells, Cultured
Graft vs Host Disease
Graft vs Host Reaction
Interferon-gamma
Interleukin-17
Mice
Mice, Inbred Strains
Mice, Transgenic
Nuclear Receptor Subfamily 1, Group F, Member 3
Severity of Illness Index
Survival Analysis
T-Lymphocyte Subsets
T-Lymphocytes, Helper-Inducer
Th1 Cells
Time Factors
Tumor Necrosis Factor-alpha
Whole Body Imaging