Selective requirement for CD40-CD154 in drug-induced type 1 versus type 2 responses to trinitrophenyl-ovalbumin

Stefan Nierkens, Pauline Van Helden, Marianne Bol, Rob Bleumink, Peter Van Kooten, Seema Ramdien-Murli, Louis Boon, Raymond Pieters

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

31 Citaten (Scopus)

Samenvatting

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-γ 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-α 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.

Originele taal-2Engels
Pagina's (van-tot)3747-3754
Aantal pagina's8
TijdschriftJournal of Immunology
Volume168
Nummer van het tijdschrift8
DOI's
StatusGepubliceerd - 15 apr. 2002
Extern gepubliceerdJa

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