Helper T-Cell Differentiation in Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Review

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapeutic option for many malignant diseases. However, the efficacy of allo-HSCT is limited by the occurrence of destructive graft-versus-host disease (GVHD). Since allogeneic T cells are the driving force in the development of GVHD, their activation, proliferation, and differentiation are key factors to understanding GVHD pathogenesis. This review focuses on one critical aspect: the differentiation and function of helper T (Th) cells in acute GVHD. We first summarize well-established subsets including Th1, Th2, Th17, and T-regulatory cells; their flexibility, plasticity, and epigenetic modification; and newly identified subsets including Th9, Th22, and T follicular helper cells. Next, we extensively discuss preclinical findings of Th-cell lineages in GVHD: the networks of transcription factors involved in differentiation, the cytokine and signaling requirements for development, the reciprocal differentiation features, and the regulation of microRNAs on T-cell differentiation. Finally, we briefly summarize the recent findings on the roles of T-cell subsets in clinical GVHD and ongoing strategies to modify T-cell differentiation for controlling GVHD in patients. We believe further exploration and understanding of the immunobiology of T-cell differentiation in GVHD will expand therapeutic options for the continuing success of allo-HSCT.

Keywords

Allo-HSCT GVL GVHD T-cell differentiation 

Notes

Acknowledgments

We thank the current and past members of Dr. Yu’s laboratory for their intellectual input and hard work. The research in Dr. Yu’s laboratory has been supported in part by grants from the National Institutes of Health (R01s CA11816, CA143812, AI 082685, and CA169116).

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Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2014

Authors and Affiliations

  • Jianing Fu
    • 1
    • 3
  • Jessica Heinrichs
    • 2
    • 3
  • Xue-Zhong Yu
    • 3
    • 4
  1. 1.Cancer Biology PhD Program, H. Lee Moffitt Cancer Center and Research InstituteUniversity of South FloridaTampaUSA
  2. 2.Department of Pathology and Cell BiologyUniversity of South FloridaTampaUSA
  3. 3.Department of Microbiology and ImmunologyMedical University of South CarolinaCharlestonUSA
  4. 4.Department of MedicineMedical University of South CarolinaCharlestonUSA

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