CD28 co-stimulation stabilizes the expression of the CD40 ligand on T cells.
The ligand for CD40 (CD40L) is a protein which is expressed on CD4 T cells following their activation: CD40-CD40L interactions are absolutely required for the induction of T cell-dependent antibody responses, yet little is known about the mechanisms whereby CD40L+ primary T cells activate naive B cells, since the protein is only transiently expressed and is rapidly down-regulated following T cell-B cell contact. We show here, using a variety of assays, that co-stimulation of primary murine T cells via CD3 and CD28 stabilizes the expression of the CD40L protein. Firstly, T cells stimulated in this manner express higher levels of CD40L when activated in the presence of B cells, compared to CD3-activated T cells. Secondly, the CD40L expressed on CD28-co-stimulated T cells is more resistant to B cell-induced down-regulation. Finally, CD3/CD28-preactivated, rested T cells re-express higher levels of CD40L more rapidly following re-stimulation via CD3 than T cells preactivated via CD3 alone. CD3/CD28-preactivated T cells, but not CD3-activated cells, are competent to induce DNA synthesis in naive B cells, and this requires re-stimulation via CD3 and prolonged ligation of CD40. These data therefore reinforce the concept that naive T cells need to be activated initially by cognate interaction with B7-bearing antigen-presenting cells (such as dendritic cells), before becoming competent helper effector cells capable of driving B cells into proliferation via a CD40-dependent pathway.
Division of Cellular Immunology, National Institute for Medical Research, Mill Hill, London, UK.
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Johnson-Léger
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J
Christensen
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GG
Klaus
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation; D005347:Fibroblasts; D005434:Flow Cytometry; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D019013:CD40 Antigens; D023201:CD40 Ligand; D003513:Cycloheximide; D004247:DNA; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D000099192:CD69 Antigens