Involvement of brain-derived neurotrophic factor (BDNF) in MP4-induced autoimmune encephalomyelitis.
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.
Javeri
Sita
S
Department of Anatomy, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany.
Rodi
Michael
M
Tary-Lehmann
Magdalena
M
Lehmann
Paul V
PV
Addicks
Klaus
K
Kuerten
Stefanie
S
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D002531:Cerebellum / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006579:Heterozygote; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
D019208:Brain-Derived Neurotrophic Factor; D020381:Interleukin-17; D007376:Interleukin-2; C101821:MP4 protein, chimeric; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma