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

van Rijt, Leonie S; Vos, Nanda; Willart, Monique; KleinJan, Alex; Coyle, Anthony J; Hoogsteden, Henk C; Lambrecht, Bart N

doi:10.1016/j.jaci.2004.03.044

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 114, Issue 1 , Pages 166-173, July 2004

Essential role of dendritic cell CD80/CD86 costimulation in the induction, but not reactivation, of T_H2 effector responses in a mouse model of asthma☆

From ^athe Department of Pulmonary and Critical Care Medicine, Erasmus University Medical Center, Rotterdam, and ^bthe Inflammation Division, Millennium Pharmaceuticals, Boston USA

Received 20 February 2004; received in revised form 22 March 2004; accepted 29 March 2004.

Rotterdam, The Netherlands, and Boston, Mass

Abstract

Background

Airway dendritic cells (DCs) are crucial for the generation of T_H2 cells from naive T cells during sensitization and for reactivation of primed T_H2 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 T_H2 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 T_H2 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 T_H2 cells but not during restimulation of previously primed T_H2 cells in the challenge phase.

Keywords: Dendritic cells, antigen presentation, antigen processing, allergy, mouse asthma model costimulation

Abbreviations: APC, Antigen-presenting cell, BALF, Bronchoalveolar lavage fluid, CFSE, Carboxyfluorescein diacetate succinimidyl ester, CTLA4, Cytotoxic T lymphocyte–associated antigen 4, DC, Dendritic cell, LN, Lymph node, OVA, Ovalbumin-pulsed dendritic cell, TCR, T-cell receptor, WT, Wild type