Involvement of brain-derived neurotrophic factor (BDNF) in MP4-induced autoimmune encephalomyelitis Sita Javeri a , 1 , Michael Rodi a , 1 , Magdalena Tary-Lehmann b , c , Paul V. Lehmann b , c , Klaus Addicks a , Stefanie Kuerten a , ⁎ a Department of Anatomy, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany b Department of Pathology, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA c Cellular Technology Limited, 20521 Chagrin Blvd, Cleveland, OH 44122, USA Received 19 February 2010; accepted with revision 1 August 2010 Available online 24 August 2010 KEYWORDS BDNF; CNS pathology; Cytokine profile; EAE; MP4; MS 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. © 2010 Elsevier Inc. All rights reserved. 1. Introduction Brain-derived neurotrophic factor (BDNF) belongs to the nerve growth factor (NGF) family of neurotrophins and was first described by Barde et al. in 1982 [1]. In the CNS a widespread distribution of BDNF mRNA and protein has been demonstrated with high levels in the hippocampal region [2]. There are various physiological effects assigned to BDNF such Abbreviations: B6, C57BL/6; BDNF, brain-derived neurotrophic factor; BSA, bovine serum albumin; CFA, complete Freund's adjuvant; CFSE, carboxyfluorescein succinimidyl ester; CNS, central nervous system; drLN, draining lymph node; EAE, experimental autoimmune encephalomyelitis; IFA, incomplete Freund's adjuvant; HE, hematoxylin/eosin; IHC, immunohistochemistry; LFB, luxol fast blue; MBP, myelin basic protein; MOG, myelin oligodendrocyte glycoprotein; MP4, MBP–PLP fusion protein; MS, multiple sclerosis; NGF, nerve growth factor; NT, neurotrophin; OVA, ovalbumin; PBMCs, peripheral blood mononuclear cells; PBS, phosphate-buffered saline; PLP, proteolipid protein; PTX, pertussis toxin; TBS, tris-buffered saline; TMB, tetramethylbenzidine. ⁎ Corresponding author. Fax: + 49 221 478 6711. E-mail address: stefanie.kuerten@uk-koeln.de (S. Kuerten). 1 S.J. and M.R. contributed equally to this work. 1521-6616/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.clim.2010.08.001 available at www.sciencedirect.com Clinical Immunology www.elsevier.com/locate/yclim Clinical Immunology (2010) 137, 181–189