Aug, 2008
Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease
EXPERIMENTAL HEMATOLOGY
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- Volume
- 36
- Number
- 8
- First page
- 988
- Last page
- 996
- Language
- English
- Publishing type
- DOI
- 10.1016/j.exphem.2008.02.010
- Publisher
- ELSEVIER SCIENCE INC
The rote 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(+) T cells or their suppressive functions. Our data thus unequivocally demonstrate that deficiency of the four classical Th2 cytokine enhances T-cell proliferative responses and aggravates GVHD. (c) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
- Link information
- ID information
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- DOI : 10.1016/j.exphem.2008.02.010
- ISSN : 0301-472X
- Web of Science ID : WOS:000258207200009