Essential role of dendritic cell CD80/CD86 costimulation in the induction, but not reactivation, of T sub(H)2 effector responses in a mouse model of asthma

Airway dendritic cells (DCs) are crucial for the generation of T sub(H)2 cells from naive T cells during sensitization and for reactivation of primed T sub(H)2 cells on allergen challenge in mouse models of asthma. It is unknown whether CD80/CD86 costimulation is necessary during both phases of the...

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Published in:Journal of allergy and clinical immunology 2004-07, Vol.114 (1), p.166-173
Main Authors: Van Rijt, LS, Vos, N, Willart, M, KleinJan, A, Coyle, A J, Hoogsteden, H, Lambrecht, B N
Format: Article
Language:English
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Summary:Airway dendritic cells (DCs) are crucial for the generation of T sub(H)2 cells from naive T cells during sensitization and for reactivation of primed T sub(H)2 cells on allergen challenge in mouse models of asthma. It is unknown whether CD80/CD86 costimulation is necessary during both phases of the response because primed T cells rely less on costimulatory molecules compared with naive T cells. We sought to study the contribution of CD80/CD86 costimulatory molecules on DCs during sensitization or challenge in a mouse model of asthma. Naive BALB/c mice received an intratracheal injection of ovalbumin (OVA)-pulsed DCs obtained from the bone marrow of wild-type (WT) or CD80/CD86 super(-/-) mice and were subsequently challenged with OVA aerosol to address the role of costimulation during sensitization. OVA-sensitized mice received OVA-pulsed WT or CD80/CD86 super(-/-) DCs without OVA aerosol to address the role of costimulation during challenge. WT DCs induced the proliferation and effector T sub(H)2 differentiation of naive OVA-specific T cells, whereas CD80/CD86 super(-/-) DCs induced only proliferation. Not surprisingly, WT DCs but not CD80/CD86 super(-/-) DCs induced sensitization to OVA in naive mice. In contrast, in OVA-sensitized mice intratracheal injection of CD80/CD86 super(-/-) OVA-pulsed DCs led to eosinophilic airway inflammation, goblet cell hyperplasia, and effector T sub(H)2 cytokine production that was not different from that seen after injection with WT OVA-DCs, even when the inducible costimulator ICOS was blocked or cytotoxic T lymphocyte-associated antigen 4 immunoglobulin was given. CD80/CD86 costimulation on DCs is only necessary during priming of naive T cells into T sub(H)2 cells but not during restimulation of previously primed T sub(H)2 cells in the challenge phase.
ISSN:0091-6749
DOI:10.1016/j.jaci.2004.03.044