CD40 ligand induction on T cell subsets by peptide-presenting B cells: implications for development of the primary T and B cell response.
Recent data suggest that CD40 ligand (CD40L)-CD40 interactions are essential for up-regulation of costimulatory activity on APC and that efficient induction of CD40L may be pivotal to the success of a CD4 T cell response. CD40L is regulated primarily by TCR signaling, but high level expression on a naive T cell appears to require additional interactions between T cell coreceptors and APC accessory molecules. The data reported here show that resting B cells presenting peptide Ag, in contrast to both dendritic cells and preactivated B cells, induce very little CD40L on naive CD4 cells, which in turn is insufficient to promote APC costimulatory activity. We also show, however, that previously activated effector T cells have enhanced responsiveness to Ag when accessory molecule help is limiting and consequently can express high levels of CD40L after interaction with resting B cells. High level CD40L expression correlated with B cell activation and up-regulation of costimulatory activity; however, blocking studies showed that CD40L was only partially responsible for these phenomena. These studies reinforce the notion that resting B cells may be tolerogenic for naive CD4 cells in part because of inefficient CD40L induction. The data also suggest that a successful primary T cell response will only occur if either the initial interaction is with a dendritic cell followed by subsequent interactions of the effector T cells with resting APC or if nonspecific inflammatory stimuli up-regulate accessory molecule expression on resting APC before an encounter with the naive T cell.
Jaiswal
A I
AI
Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Croft
M
M
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D015854:Up-Regulation
D000941:Antigens; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D023201:CD40 Ligand