Abstract
We previously showed that transplantation with IL-21R gene-deficient splenocytes resulted in less severe graft-versus-host disease (GVHD) than was observed with wild type splenocytes. In this study, we sought to find mechanism(s) explaining this observation. Recipients of donor CD4(+) T cells lacking IL-21R exhibited diminished GVHD symptoms, with reduced inflammatory cell infiltration into the liver and intestine, leading to prolonged survival. After transplantation, CD4(+) T cell numbers in the spleen were reduced, and MLR and cytokine production by CD4(+) T cells were impaired. These results suggest that IL-21 might promote GVHD through enhanced production of effector CD4(+) T cells. Moreover, we found that CD25 depletion altered neither the impaired MLR in vitro nor the ameliorated GVHD symptoms in vivo. Thus, the attenuated GVHD might be caused by an impairment of effector T cell differentiation itself, rather than by an increase in regulatory T cells and suppression of effector T cells.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow Transplantation / immunology
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Bone Marrow Transplantation / pathology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / pathology*
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CD4-Positive T-Lymphocytes / transplantation
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Cell Movement / genetics
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Cell Movement / immunology
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Cells, Cultured
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Female
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Gene Deletion*
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Graft vs Host Disease / immunology*
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Graft vs Host Disease / pathology*
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Graft vs Host Disease / prevention & control
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Immunophenotyping
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Inflammation Mediators / physiology
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Interleukin-21 Receptor alpha Subunit / deficiency*
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Interleukin-21 Receptor alpha Subunit / genetics*
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Interleukin-21 Receptor alpha Subunit / physiology
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Interleukins / physiology
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Mice, Knockout
Substances
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Il21r protein, mouse
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Inflammation Mediators
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Interleukin-21 Receptor alpha Subunit
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Interleukins
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interleukin-21