Normal Th1 development following long-term therapeutic blockade of CD154-CD40 in experimental autoimmune encephalomyelitis.
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.
Howard
Laurence M
LM
Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Ostrovidov
Serge
S
Smith
Cassandra E
CE
Dal Canto
Mauro C
MC
Miller
Stephen D
SD
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D019013:CD40 Antigens / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D011991:Receptors, Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016207:Cytokines; D008565:Membrane Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D010455:Peptides; D016201:Receptors, Lymphocyte Homing; D011991:Receptors, Virus; C435023:myelin proteolipid protein (139-151); C066100:poliovirus receptor