IL‐15‐dependent CD8+CD122+ T cells ameliorate experimental autoimmune encephalomyelitis by modulating IL‐17 production by CD4+ T cells

Interleukin‐15 (IL‐15) is an inflammatory cytokine whose role in autoimmune diseases has not been fully elucidated. Th17 cells have been shown to play critical roles in experimental autoimmune encephalomyelitis (EAE) models. In this study, we demonstrate that blockade of IL‐15 signaling by TMβ‐1 mAb...

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Bibliographic Details
Published in:European journal of immunology 2014-11, Vol.44 (11), p.3330-3341
Main Authors: Yu, Ping, Bamford, Richard N., Waldmann, Thomas A.
Format: Article
Language:English
Subjects:
Adoptive Transfer
Animals
Antibodies, Monoclonal - immunology
Antibodies, Neutralizing - immunology
CD8+CD122+ T cells
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - transplantation
Cell Differentiation - immunology
Cell Proliferation
Cells, Cultured
Coculture Techniques
Encephalomyelitis, Autoimmune, Experimental - immunology
Experimental autoimmune encephalomyelitis
Interleukin-15 - antagonists & inhibitors
Interleukin-15 - immunology
Interleukin-17 - biosynthesis
Interleukin-17 - immunology
Interleukin-17 - metabolism
Interleukin-2 Receptor beta Subunit - immunology
Interleukin‐15
Interleukin‐17
Killer Cells, Natural - immunology
Killer Cells, Natural - transplantation
Lymphocyte Activation - immunology
Lymphocyte Depletion
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Multiple sclerosis
Signal Transduction - immunology
Th17 Cells - cytology
Th17 Cells - immunology
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Summary:Interleukin‐15 (IL‐15) is an inflammatory cytokine whose role in autoimmune diseases has not been fully elucidated. Th17 cells have been shown to play critical roles in experimental autoimmune encephalomyelitis (EAE) models. In this study, we demonstrate that blockade of IL‐15 signaling by TMβ‐1 mAb treatment aggravated EAE severity. The key mechanism was not NK‐cell depletion but depletion of CD8+CD122+ T cells. Adoptive transfer of exogenous CD8+CD122+ T cells to TMβ‐1‐treated mice rescued animals from severe disease. Moreover, transfer of preactivated CD8+CD122+ T cells prevented EAE development and significantly reduced IL‐17 secretion. Naïve effector CD4+CD25− T cells cultured with either CD8+CD122+ T cells from wild‐type mice or IL‐15 transgenic mice displayed lower frequencies of IL‐17A production with lower amounts of IL‐17 in the supernatants when compared with production by effector CD4+CD25− T cells cultured alone. Addition of a neutralizing antibody to IL‐10 led to recovery of IL‐17A production in Th17 cultures. Furthermore, coculture of CD8+CD122+ T cells with effector CD4+ T cells inhibited their proliferation significantly, suggesting a regulatory function for IL‐15 dependent CD8+CD122+ T cells. Taken together, these observations suggest that IL‐15, acting through CD8+CD122+ T cells, has a negative regulatory role in reducing IL‐17 production and Th17‐mediated EAE inflammation.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201444675