Work

In VITRO Polarized TH17 Cells Induce Severe Acute Graft-Versus-Host Disease

Year: 2009

Type: article

Abstract: Contribution of different T cell subsets in the development of graft-versus-host disease (GVHD) is an active area of research. T helper type-1 (Th1) cells were believed to be the most important CD4 T cell subset to induce GVHD through inflammatory cytokines including IFNγ and TNFα. However, the concept was seriously challenged by recent findings that T cells deficient for IFNγ, Stat4 or T-bet caused exacerbated GVHD. These results indicate that Th1 subset is not required for the induction of GVHD and other Th subsets are sufficient. Th17 is a newly identified T cell lineage that secretes IL-17A among other pro-inflammatory cytokines. Th17 cells play a critical role in autoimmune diseases, including causing a systemic autoimmune disorder resembling GVHD. However, the role of Th17 cells in the pathogenesis of classical GVHD remains unclear. In the current study, by transferring in vitro generated Th17 cells together with donor bone marrow into lethally irradiated allogeneic recipients, we demonstrated that allogeneic Th17 cells were highly pathogenic to induce GVHD, more so than naïve or Th1 controls. The same Th17 cells, however, caused no pathology in the syngeneic recipients, indicating antigen-activation was required for these cells to induce GVHD. High potency of Th17 cells in the induction of GVHD was correlated with their superior ability to expand and to infiltrate in GVHD target organs. After transfer into recipients, Th17 cells produced significant levels of IFNγ and TNFα besides IL-17A. Furthermore, IFNγ KO Th17 cells had reduced ability to cause GVHD compared to wild type (WT) Th17 cells, indicating that IFNγ also contributes to the pathogenicity of Th17 cells. Our findings show that both Th1 and Th17 cells participate in the pathogenesis of acute GVHD.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2008.12.373

Authors: C. Iclozan, C. Liu, Y. Yu, T. Yi, C. Anasetti, X.-Z. Yu

Institutions: Moffitt Cancer Center, University of Florida, City Of Hope National Medical Center, University of South Florida

Language: English

Topic: Hematopoietic Stem Cell Transplantation

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,650