Recognition of pollen-derived phosphatidyl-ethanolamine by human CD1d-restricted γδ T cells

Background: Evidences from mice and human beings indicate that γδ T cells could be relevant in recognition of stress-induced self and/or yet unidentified inhaled foreign antigens. Their specificity differs from classic MHC-restricted αβ T cells and involves the immunoglobulin-like structure of the γδ T-cell receptor with the recognition of small organic molecules, alkylamines, and self lipid compounds presented by CD1 ⁺ dendritic cells. Objective: Because CD1 receptors are mainly devoted to lipid antigen presentation, we sought to determine whether exogenous pollen membrane lipids may act as allergens for CD1-restricted γδ T cells. Methods: Peripheral blood and nasal mucosa-associated γδ T cells were cloned from normal controls and cypress-sensitive subjects and tested for their antigen specificity and CD1-restriction with phospholipids extracted from tree pollen grains, as well with other natural or synthetic compounds. Phospholipid reactivity of cloned γδ T cells was measured by mean of proliferative response and cytokine release as well as by testing their helper activity on IgE production in vitro and in vivo. Results: Cloned γδ T lymphocytes from subjects with allergy, but not normal controls, were found to recognize pollen-derived phosphatidyl-ethanolamine (PE) in a CD1d-restricted fashion. Only 16:0/18:2 and 18:2/18:2 PE were stimulatory, whereas no response was recorded for disaturated PE, phosphatidylcholine, neutral lipids, or protein extract. Proliferating clones secreted both T _H1-type and T _H2-type cytokines and drove IgE production in vitro and in vivo. Conclusion: CD1d-restricted γδ T cells specific for phospholipids can represent a key mucosal regulatory subset for the control of early host reactivity against tree pollens. Clinical implications: By knowing how lipid allergen constituents interact with mucosal immune system, we can expand our possibilities in diagnostic and therapeutic interventions.