CD40L blockade prevents autoimmune encephalomyelitis and hampers TH1 but not TH2 pathway of T cell differentiation.
Although it is well established that CD40 and its ligand (CD40L) play pivotal roles in the development of humoral immunity, their roles in cell-mediated immunity and cell-mediated autoimmune diseases are not well defined. We report here that CD40:CD40L interaction is crucial for the development of experimental autoimmune encephalomyelitis (EAE), a prototype TH1-cell mediated autoimmune disease. Specific blockade of CD40L at the time of immunization markedly suppressed the incidence, mortality, day of onset, and clinical scores of EAE in (PLJ x SJL) F1 mice. Importantly, the disease suppression was not associated with anergy or deletion of autoreactive T cells but was accompanied by a drastic alteration of their cytokine profiles. The production of interferon (IFN)-gamma was markedly suppressed while that of interleukin (IL)-4 enhanced. These results suggest that CD40:CD40L interaction plays important roles in the differentiation of autoreactive TH1 versus TH2 cells in vivo, and that CD40L blockade is effective in preventing autoimmune encephalomyelitis.
Samoilova
E B
EB
Institute for Human Gene Therapy, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Horton
J L
JL
Zhang
H
H
Chen
Y
Y
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005260:Female; D007108:Immune Tolerance; D007114:Immunization; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology; D011994:Recombinant Proteins; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D019138:Antibodies, Blocking; D000945:Antigens, Differentiation, T-Lymphocyte; D019013:CD40 Antigens; D016207:Cytokines; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D011994:Recombinant Proteins; D023201:CD40 Ligand