IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis.
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IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis. / Huber, Magdalena; Heink, Sylvia; Pagenstecher, Axel; Reinhard, Katharina; Ritter, Josephine; Visekruna, Alexander; Guralnik, Anna; Bollig, Nadine; Jeltsch, Katharina; Heinemann, Christina; Wittmann, Eva; Buch, Thorsten; Olivia, Prazeres Da Costa; Brüstle, Anne; Brenner, Dirk; Mak, Tak W; Mittrücker, Hans Willi; Tackenberg, Björn; Kamradt, Thomas; Lohoff, Michael.
In: J CLIN INVEST, Vol. 123, No. 1, 1, 2013, p. 247-260.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis.
AU - Huber, Magdalena
AU - Heink, Sylvia
AU - Pagenstecher, Axel
AU - Reinhard, Katharina
AU - Ritter, Josephine
AU - Visekruna, Alexander
AU - Guralnik, Anna
AU - Bollig, Nadine
AU - Jeltsch, Katharina
AU - Heinemann, Christina
AU - Wittmann, Eva
AU - Buch, Thorsten
AU - Olivia, Prazeres Da Costa
AU - Brüstle, Anne
AU - Brenner, Dirk
AU - Mak, Tak W
AU - Mittrücker, Hans Willi
AU - Tackenberg, Björn
AU - Kamradt, Thomas
AU - Lohoff, Michael
PY - 2013
Y1 - 2013
N2 - IL-17-producing CD8+ T (Tc17) cells are detectible in multiple sclerosis (MS) lesions; however, their contribution to the disease is unknown. To identify functions of Tc17 cells, we induced EAE, a murine model of MS, in mice lacking IFN regulatory factor 4 (IRF4). IRF4-deficient mice failed to generate Tc17 and Th17 cells and were resistant to EAE. After adoptive transfer of WT CD8+ T cells and subsequent immunization for EAE induction in these mice, the CD8+ T cells developed a Tc17 phenotype in the periphery but could not infiltrate the CNS. Similarly, transfer of small numbers of WT CD4+ T cells alone did not evoke EAE, but when transferred together with CD8+ T cells, IL-17-producing CD4+ (Th17) T cells accumulated in the CNS and mice developed severe disease. Th17 accumulation and development of EAE required IL-17A production by CD8+ T cells, suggesting that Tc17 cells are required to promote CD4+ T cell-mediated induction of EAE. Accordingly, patients with early-stage MS harbored a greater number of Tc17 cells in the cerebrospinal fluid than in peripheral blood. Our results reveal that Tc17 cells contribute to the initiation of CNS autoimmunity in mice and humans by supporting Th17 cell pathogenicity.
AB - IL-17-producing CD8+ T (Tc17) cells are detectible in multiple sclerosis (MS) lesions; however, their contribution to the disease is unknown. To identify functions of Tc17 cells, we induced EAE, a murine model of MS, in mice lacking IFN regulatory factor 4 (IRF4). IRF4-deficient mice failed to generate Tc17 and Th17 cells and were resistant to EAE. After adoptive transfer of WT CD8+ T cells and subsequent immunization for EAE induction in these mice, the CD8+ T cells developed a Tc17 phenotype in the periphery but could not infiltrate the CNS. Similarly, transfer of small numbers of WT CD4+ T cells alone did not evoke EAE, but when transferred together with CD8+ T cells, IL-17-producing CD4+ (Th17) T cells accumulated in the CNS and mice developed severe disease. Th17 accumulation and development of EAE required IL-17A production by CD8+ T cells, suggesting that Tc17 cells are required to promote CD4+ T cell-mediated induction of EAE. Accordingly, patients with early-stage MS harbored a greater number of Tc17 cells in the cerebrospinal fluid than in peripheral blood. Our results reveal that Tc17 cells contribute to the initiation of CNS autoimmunity in mice and humans by supporting Th17 cell pathogenicity.
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Knockout
KW - Adoptive Transfer
KW - CD8-Positive T-Lymphocytes/immunology/metabolism/pathology
KW - Central Nervous System/immunology/metabolism/pathology
KW - Encephalomyelitis, Autoimmune, Experimental/genetics/immunology/metabolism/pathology
KW - Interferon Regulatory Factors/genetics/immunology/metabolism
KW - Interleukin-17/genetics/immunology/metabolism
KW - Th17 Cells/immunology/metabolism/pathology/transplantation
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Knockout
KW - Adoptive Transfer
KW - CD8-Positive T-Lymphocytes/immunology/metabolism/pathology
KW - Central Nervous System/immunology/metabolism/pathology
KW - Encephalomyelitis, Autoimmune, Experimental/genetics/immunology/metabolism/pathology
KW - Interferon Regulatory Factors/genetics/immunology/metabolism
KW - Interleukin-17/genetics/immunology/metabolism
KW - Th17 Cells/immunology/metabolism/pathology/transplantation
M3 - SCORING: Journal article
VL - 123
SP - 247
EP - 260
JO - J CLIN INVEST
JF - J CLIN INVEST
SN - 0021-9738
IS - 1
M1 - 1
ER -
