CD40 stimulation in vivo does not inhibit CD4+ T cell tolerance to soluble antigens.
Anergy, or T cell unresponsiveness to antigen, is one mechanism of T cell tolerance. However, the signaling events that lead to immune tolerance are not well understood. A common assumption is that soluble antigens, such as food antigens, are poor immunogens and induce tolerance because they fail to upregulate co-stimulatory molecules on the professional APC. Engagement of CD40 through a stimulatory antibody causes the upregulation of these costimulatory molecules. Using a CD4+ T cell adoptive transfer model specific to ovalbumin (OVA), we show that after upregulation of CD86 on APC through CD40 stimulation in vivo, T cells from OVA-fed mice remain refractory to proliferation, interleukin (IL)-2 and interferon (IFN)-gamma production. We conclude that upregulation of CD86 alone does not inhibit oral tolerance induction of CD4+ T cells, indicating that additional signals are involved in the decision process for CD4+ T cells to commit to tolerance versus sensitization. Our data challenge the belief that reconstitution of a costimulatory signal in the presence of soluble antigen is sufficient to override T cell tolerance and anergy.
Sun
Jiaren
J
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
Van Houten
Nancy
N
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen; D015704:CD4 Antigens; D019013:CD40 Antigens / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000187:drug effects / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051940:B7-2 Antigen; D015704:CD4 Antigens; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D010047:Ovalbumin