Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease.

Experimental Hematology
Isao TawaraPavan Reddy

Abstract

The role of T helper (Th) 1 and Th2 polarization in acute graft-vs-host-disease (GVHD) is unclear. We investigated the role of Th2 cytokine secretion by utilizing donor T cells that cannot make interleukin (IL)-4, IL-5, IL-9, and IL-13 from quadruple cytokine-deficient (Quad-KO) animals in a well-characterized BALB/c-->C57BL/6 model of allogeneic bone marrow transplantation. B6 recipients of BALB/c Quad-KO T cells demonstrated greater clinical severity, target organ damage, and mortality from GVHD than recipients of BALB/c wild-type (WT) T cells. When compared with donor T cells that are deficient in signal transducers and activators of transcription 6 signaling or the signature Th2 cytokine, IL-4, Quad-KO T cells demonstrated greater GVHD mortality. Mechanistic studies demonstrated that Quad-KO T cells demonstrated enhanced T-cell proliferation than WT T cells when stimulated with either allogeneic antigen-presenting cells or with nonspecific stimuli, such as anti-CD3 monoclonal antibody. Quad-KO T cells also secreted greater amounts of Th1 cytokines and IL-17 compared to WT T cells. Deficiency of Th2 cytokines, however, did not alter the allospecific cytotoxic responses, the numbers of immunoregulatory CD4(+)CD25(+) Foxp3(+) ...Continue Reading

Citations

Aug 21, 2013·International Journal of Hematology·Akiyoshi Takami
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Sep 9, 2015·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Alina SchrederChristian Koenecke
Aug 30, 2011·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Isao TawaraPavan Reddy
Oct 19, 2017·The Journal of Experimental Medicine·Abdulraouf RamadanSophie Paczesny
Jan 11, 2011·Bone Marrow Transplantation·J L EspinozaUNKNOWN Japan Marrow Donor Program
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