Normal Th1 development following long-term therapeutic blockade of CD154-CD40 in experimental autoimmune encephalomyelitis

• Published in: The Journal of clinical investigation 2002, Vol.109 (2), p.233-241
• Main Authors: Howard, Laurence M, Ostrovidov, Serge, Smith, Cassandra E, Dal Canto, Mauro C, Miller, Stephen D
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - therapeutic use; CD40 Antigens - immunology; Cell Division - drug effects; Cytokines - secretion; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Female; Humans; Hypersensitivity, Delayed - immunology; Membrane Proteins; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Myelin Proteolipid Protein - immunology; Peptide Fragments - immunology; Peptides - immunology; Receptors, Lymphocyte Homing - immunology; Receptors, Virus - immunology; T-Lymphocytes - immunology; Th1 antigen; Th1 Cells - immunology; Time Factors
• ISSN: 0021-9738
• DOI: 10.1172/JCI0214374

Experimental autoimmune encephalomyelitis (EAE) is a Th1-mediated demyelinating disease of the CNS with similarities to multiple sclerosis. We and others have shown that a short-term course of anti-CD154 mAb treatment to block CD154-CD40 interactions can be used to prevent or even treat ongoing PLP139-151-induced relapsing EAE. However, little is known of the long-term effects of CD154 blockade on the development of antigen-specific T cell function. Here, we show that short-term treatment with anti-CD154 at the time of PLP139-151/CFA immunization inhibits clinical disease for up to 100 days after immunization. At this point, comparable numbers of Th1 cells are observed in anti-CD154 and control Ig-treated mice, as assessed by antigen-specific ELISPOT assays. Thus, the long-term Th1/Th2 balance is largely unaffected. Inflammatory responses are diminished in anti-CD154-treated mice, as indicated by reduced in vivo delayed-type hypersensitivity and reduced levels of splenic IFN-gamma secretion in vitro. However, upon adoptive transfer of T cells isolated from the spleens of anti-CD154-treated mice, these cells contributed as effectively to clinical disease as those obtained from control-treated mice. Thus, anti-CD154 therapy leads to long-term therapeutic efficacy without exerting a long-term influence on Th1 development.