Graft versus host disease (GVHD) is a refractory complication of allogeneic hematopoietic stem cell transplantation for the treatment of malignant and non-malignant hematopoietic diseases. Inflammatory cascade responses and cellular immune reactions are the major factors underlying GVHD pathogenesis. Cells producing the cytokine, interleukin (IL)-21 are crucial players involved in injured tissues in GVHD patients. Besides T helper 17 cells, follicular T helper (Tfh) cells are a new source of IL-21 and play a vital role in GVHD pathogenesis. Tfh cell function is mostly regulated by T-follicular regulatory (Tfr) cells that are also located in the germinal center. This review highlights recent advances in the role of Tfh and Tfr cell function in GVHD pathogenesis. New insights are provided into the potential for clinical application in GVHD prevention and treatment.
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