T cell and antibody responses in remitting–relapsing experimental autoimmune encephalomyelitis in (C57BL/6ÂSJL) F1 mice $ Guang-Xian Zhang a , Shuo Yu a , Bruno Gran a , Jifen Li a , Divina Calida a , Elvira Ventura a , Xiaohan Chen b , Abdolmohamad Rostami a, * a Department of Neurology, Thomas Jefferson University, 1025 and Walnut Street, Suite 310, Philadelphia, PA 19107-5083, USA b Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA USA Received 2 May 2003; received in revised form 3 September 2003; accepted 16 October 2003 Abstract To characterize T cell and antibody responses in remitting–relapsing experimental autoimmune encephalomyelitis (RR-EAE), we compared myelin oligodendrocyte glycoprotein (MOG)-induced RR-EAE in C57BL/6 (B6) Â SJL (F1) mice and chronic-progressive EAE (CP-EAE) in B6 mice at week 8 p.i. when clinical scores were comparable. Although these two strains exhibited similar inflammation/ demyelination pattern and MOG-induced T cell responses, RR-EAE mice produced significantly higher levels of anti-MOG IgG1/IgG2a antibodies. Further, lymphocytes of RR-EAE mice proliferated vigorously to the secondary epitope myelin basic protein (MBP) 1 –11. These results support a potential involvement of anti-MOG antibodies and epitope spreading in T cell responses in the development of MOG- induced RR-EAE model. D 2004 Elsevier B.V. All rights reserved. Keywords: Cytokines; Antibodies; Epitope spreading; Remitting – relapsing; Multiple sclerosis 1. Introduction Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is a T cell-mediated autoimmune disease of the central nervous system (CNS) (Martin and McFarland, 1995). EAE can be induced by immunization with CNS antigens, and various immuniza- tion protocols induce a multitude of EAE forms in several species. Remitting – relapsing experimental autoimmune en- cephalomyelitis (RR-EAE) is an ideal model for the study of autoimmune mediated demyelination and immunoregulato- ry events leading to relapses in human multiple sclerosis. In mice, RR-EAE could be induced in SJL mice with spinal cord homogenate (Lublin et al., 1981) or proteolipid protein (PLP) peptide 139–151 (PLP139–151), PLP178–191, my- elin basic protein (MBP) 87–116 (Takacs et al., 1997), or myelin oligodendrocyte glycoprotein (MOG) 92–106 (Tsu- noda et al., 2000). RR-EAE was also induced in B10.PL mice with MBP1 – 11 (Benson et al., 1999), or SJL Â PLJ F1 mice with MBP and its peptides (Samson and Smilek, 1995). MOG is a quantitatively minor component of CNS myelin (Linington et al., 1984; Pham-Dinh et al., 1993) located at the surface of oligodendrocyte membranes and the outer lamellae of the myelin sheath (Birling et al., 1993; Brunner et al., 1989; Lebar et al., 1986). This location makes MOG an important target in antibody-mediated phagocytosis and demyelination (Amor et al., 1994; Diaz-Villoslada et al., 1999; Raine et al., 1999; Van der Goes et al., 1999). MOG peptide 35–55 (MOG35–55) has been extensively used in the induction of EAE in C57BL/6 (B6) mice, which develop chronic progressive EAE (CP-EAE) (Mendel et al., 1995), but not RR-EAE. MOG35–55 has been used in the attempt to induce RR-EAE in PL/J mice. However, after one initial immunization and two boosters over several weeks, only 3/ 10 of mice developed a delayed (up to 3 months post immunization), atypical clinical course of RR-EAE (Kerlero de Rosbo et al., 1995). A MOG35–55-MAP peptide has 0165-5728/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jneuroim.2003.10.057 Abbreviations: RR-EAE, remitting – relapsing experimental autoim- mune encephalomyelitis; CP-EAE, chronic progressive EAE; MBP, myelin basic protein; MNCs, mononuclear cells; MOG, myelin oligodendrocyte glycoprotein; PLP, proteolipid protein. $ The study has been presented at the 55th Annual meeting of American Academy of Neurology, Honolulu, Hawaii, March 29–April 5, 2003. * Corresponding author. Tel.: +1-215-955-8100; fax: +1-215-955- 1390. E-mail address: a.m.rostami@jefferson.edu (A. Rostami). www.elsevier.com/locate/jneuroim Journal of Neuroimmunology 148 (2004) 1 – 10