Essential role of dendritic cell CD80/86 costimulation in the induction, but not reactivation, of TH2 effector responses in a mouse model of asthma

Background: Airway dendritic cells (DCs) are crucial for the generation of T(H)2 cells from naive T cells during sensitization and for reactivation of primed T(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. 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(H)2 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(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. Conclusion: CD80/CD86 costimulation on DCs is only necessary during priming of naive T cells into T(H)2 cells but not during restimulation of previously primed T(H)2 cells in the challenge phase.