Antigen-specific and nonspecific determinants of cytokine production during topical sensitization of mice to chemical allergens

Artin Moussavi, Rebecca J. Dearman, Ian Kimber, Kenn C. Daniel, David M. Kemeny

    Research output: Contribution to journalArticlepeer-review


    Background: Topical exposure to chemical allergens such as trimellitic anhydride or 1-chloro-2,4-dinitrochlorobenzene results in the accumulation of dendritic cells (DCs) and subsequent rapid up-regulation of CD4 T-cell proliferation and cytokine secretion within draining lymph nodes. Objective: We investigated the contribution of antigen-specific and CD40 ligand (CD40L)-mediated signals to chemical allergen-induced CD4 T-cell growth and cytokine production. Methods: DCs enriched from lymph nodes of allergen-challenged animals by metrizamide centrifugation were used to stimulate cytokine and proliferative responses by magnetic immunobead-sorted CD4 T cells primed in vivo with the same or unrelated allergen. Cultures of DCs and T cells were supplemented with antibodies that block IL-12 and CD40L activity. Results: Proliferation of CD4 T cells was stimulated by DCs primed with the same but not unrelated antigen, whereas IFN-γ, IL-12, and IL-10 secretion were provoked equally well by DCs primed with either hapten. Blockade of CD40L engagement abrogated production of IFN-γ (80%) and IL-12 (95%) under antigen-nonspecific stimulatory conditions. In contrast, IL-10 secretion was enhanced after CD40L blockade under both antigen-specific and nonspecific conditions. Primary CD4 T cells activated by mitogen were also influenced by DCs in the same way. Conclusion: These results show that during the development of chemical sensitization emerging CD4 T-cell growth and cytokine production are regulated by independent mechanisms requiring antigen presentation and CD40 signaling, respectively.
    Original languageEnglish
    Pages (from-to)357-368
    Number of pages11
    JournalJournal of Allergy and Clinical Immunology
    Issue number2
    Publication statusPublished - 2000


    • CD4 T lymphocyte
    • CD40 ligand
    • Chemical allergen
    • Dendritic cell
    • IFN-γ
    • IL-12


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