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 ⍺β 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.

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.

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.

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.

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.

By knowing how lipid allergen constituents interact with mucosal immune system, we can expand our possibilities in diagnostic and therapeutic interventions.