Selective requirement for CD40-CD154 in drug-induced type 1 versus type 2 responses to trinitrophenyl-ovalbumin.
CD154 is transiently expressed by activated T cells and interacts with CD40 on B cells, dendritic cells, macrophages, and monocytes. This costimulatory receptor-ligand couple seems decisive in Ag-driven immune responses but may be differentially involved in type 1 vs type 2 responses. We studied the importance of CD40-CD154 in both responses using the reporter Ag popliteal lymph node assay in which selectively acting drugs generate clearly polarized type 1 (streptozotocin) or type 2 (D-penicillamine, diphenylhydantoin) responses to a constant coinjected Ag in the same mouse strain. Treatment of mice with anti-CD154 reduced characteristic immunological parameters in type 2 responses (B and CD4(+) T cell proliferation, IgG1 and IgE Abs, and IL-4 secretion) and only slightly affected the type 1 response (small decrease in IFN-gamma production, influx of CD11c(+) and F4/80(+) cells, and prevention of architectural disruption of the lymph node, but no effect on IgG2a Ab and TNF-alpha secretion or B and CD4(+) T cell proliferation). The findings indicate that the CD40-CD154 costimulatory interaction is a prerequisite in drug-induced type 2 responses and is only marginally involved in type 1 responses. The observed expression patterns of CD80 and CD86 on different APC (B cells in type 2 and dendritic cells in type 1) may be responsible for this discrepancy.
Nierkens
Stefan
S
Department of Immunotoxicology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands. s.nierkens@iras.uu.nl
van Helden
Pauline
P
Bol
Marianne
M
Bleumink
Rob
R
van Kooten
Peter
P
Ramdien-Murli
Seema
S
Boon
Louis
L
Pieters
Raymond
R
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000378:metabolism; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand / Q000276:immunology / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D007106:Immune Sera / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology*; D010396:Penicillamine / Q000008:administration & dosage; D010672:Phenytoin / Q000008:administration & dosage; D010851:Picrates / Q000008:administration & dosage / Q000276:immunology; D013311:Streptozocin / Q000008:administration & dosage; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D006241:Haptens; D007106:Immune Sera; D008562:Membrane Glycoproteins; D010851:Picrates; C038600:trinitrophenyl-ovalbumin; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand; D013311:Streptozocin; D010672:Phenytoin; D010047:Ovalbumin; C005858:picric acid; D010396:Penicillamine