Activated Leukocyte Cell Adhesion Molecule Stimulates the T-Cell Response in Allergic Asthma

Rationale: The activated leukocyte cell adhesion molecule (ALCAM) is a cluster of differentiation 6 ligand that is important for stabilizing the immunological synapse and inducing T-cell activation and proliferation. Objectives: In this study, we investigated the role of ALCAM in the development of inflammation in allergic asthma. Methods: An ovalbumin (OVA)-induced allergic asthma model was established in wild-type (WT) and ALCAM-deficient (ALCAM(-/-)) mice. T-cell proliferation was evaluated in cocultures with dendritic cells (DCs). Bone marrow-derived dendritic cells (BMDCs) from WT and ALCAM(-/-) mice were cultured and adoptively transferred to OT-II mice for either OVA sensitization or challenge. An antiALCAM antibody was administered to assess its therapeutic potential. ALCAM concentrations in the sputum and serum of children with asthma were quantified by ELISA. Measurements and Main Results: Inflammatory responses were lower in ALCAM(-/-) mice than in WT mice, and T cells cocultured with DCs from ALCAM(-/-) mice showed reduced proliferation relative to those cocultured with DCs from WT mice. A decreased inflammatory response was observed upon adoptive transfer of BMDCs from ALCAM(-/-) mice as compared with that observed after transfer of BMDCs from WT mice. In addition, anti-ALCAM antibody-treated mice showed a reduced inflammatory response, and sputum and serum ALCAM concentrations were higher in children with asthma than in control subjects. Conclusions: ALCAM contributes to OVA-induced allergic asthma by stimulating T-cell activation and proliferation, suggesting it as a potential therapeutic target for allergic asthma.