Abstract
The role of brain-derived neurotrophic factor (BDNF) in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) is still unclear. Here we investigate the clinical course, CNS histopathology and peripheral antigen-specific immunity in MP4-induced EAE of BDNF (-/+) mice. We demonstrate that these mice displayed less severe disease compared to BDNF (+/+) mice, reflected by decreased inflammation and demyelination. In correspondence to diminished frequencies of T and B cells in CNS infiltrates, the peripheral MP4-specific T(H)1/T(H)17 response was attenuated in BDNF (-/+), but not in wild-type animals. In contrast, immunization with ovalbumin triggered similar frequencies of IFN-γ- and IL-17-secreting T cells in both groups. The cytokine secretion and proliferative activity upon mitogen stimulation did not reveal any global defect of T cell function in BDNF (-/+) mice. By influencing the antigen-specific immune response in autoimmune encephalomyelitis, BDNF may support and maintain the disease in ways that go beyond its alleged neuroprotective role.
Copyright © 2010 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Brain-Derived Neurotrophic Factor / genetics*
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / pathology
-
CD8-Positive T-Lymphocytes / immunology
-
CD8-Positive T-Lymphocytes / pathology
-
Cell Proliferation
-
Cerebellum / pathology
-
Encephalomyelitis, Autoimmune, Experimental / diagnosis
-
Encephalomyelitis, Autoimmune, Experimental / genetics
-
Encephalomyelitis, Autoimmune, Experimental / immunology*
-
Encephalomyelitis, Autoimmune, Experimental / pathology
-
Heterozygote
-
Inflammation / immunology
-
Inflammation / pathology
-
Interferon-gamma / metabolism
-
Interleukin-17 / metabolism
-
Interleukin-2 / metabolism
-
Lymph Nodes / cytology
-
Lymph Nodes / immunology
-
Lymph Nodes / metabolism
-
Lymphocyte Activation / immunology
-
Lymphocytes / immunology
-
Lymphocytes / metabolism
-
Lymphocytes / pathology
-
Mice
-
Mice, Inbred C57BL
-
Mice, Transgenic
-
Myelin Basic Protein / immunology*
-
Myelin Proteolipid Protein / immunology*
-
Recombinant Fusion Proteins / immunology*
-
Severity of Illness Index
-
Spinal Cord / pathology
-
Spleen / cytology
-
Spleen / immunology
-
Spleen / metabolism
-
Vaccination
Substances
-
Brain-Derived Neurotrophic Factor
-
Interleukin-17
-
Interleukin-2
-
MP4 protein, chimeric
-
Myelin Basic Protein
-
Myelin Proteolipid Protein
-
Recombinant Fusion Proteins
-
Interferon-gamma