Essential role of dendritic cell CD80/CD86 costimulation in the induction, but not reactivation, of TH2 effector responses in a mouse model of asthma

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Abstract

Background

Airway dendritic cells (DCs) are crucial for the generation of TH2 cells from naive T cells during sensitization and for reactivation of primed TH2 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.

Objective

We sought to study the contribution of CD80/CD86 costimulatory molecules on DCs during sensitization or challenge in a mouse model of asthma.

Methods

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−/− 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−/− DCs without OVA aerosol to address the role of costimulation during challenge.

Results

WT DCs induced the proliferation and effector TH2 differentiation of naive OVA-specific T cells, whereas CD80/CD86−/− DCs induced only proliferation. Not surprisingly, WT DCs but not CD80/CD86−/− DCs induced sensitization to OVA in naive mice. In contrast, in OVA-sensitized mice intratracheal injection of CD80/CD86−/− OVA-pulsed DCs led to eosinophilic airway inflammation, goblet cell hyperplasia, and effector TH2 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.

Conclusion

CD80/CD86 costimulation on DCs is only necessary during priming of naive T cells into TH2 cells but not during restimulation of previously primed TH2 cells in the challenge phase.

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