Differential requirements for CD28 and CD40 ligand in the induction of experimental autoimmune myasthenia gravis.
The interactions of CD28-B7 and CD40-CD40 ligand (CD40L) pathways in T cell costimulation and autoimmune disease are incompletely understood. We sought to address this issue by investigation of the genesis of acetylcholine receptor (AChR)-induced antibody-mediated experimental autoimmune myasthenia gravis (EAMG) in CD28- and CD40L-deficient mice (CD28-/-, CD40L-/-). Compared to wild-type mice, the CD28-/- mice became less susceptible, and CD40L-/- mice were completely resistant to EAMG induction. Analysis of T helper functions, reflected by cytokine responses, revealed a switch to a Th1 profile in CD28-/- mice. Consistently, levels of serum AChR-specific antibodies of the IgG1 isotype were decreased in CD28-/- mice. In the CD40L-/- mice, both Th1 and Th2 cytokine responses were diminished, and T cell-dependent AChR-reactive B cell responses were more severely impaired than in the CD28-/- mice. Thus, CD28 and CD40L are differentially required for induction of EAMG.
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Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. Fu-Dong.Shi@cnsf.ki.se
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Matusevicius
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D000595:Amino Acid Sequence; D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D023201:CD40 Ligand; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000235:genetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000209:etiology*; D011950:Receptors, Cholinergic / Q000502:physiology
D018106:CD28 Antigens; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D011950:Receptors, Cholinergic; D023201:CD40 Ligand; D007371:Interferon-gamma