Background B7/CD28 family co‐signalling molecules play a key role in regulating T cell activation and tolerance. Allergen‐specific immunotherapy (SIT) alters allergen‐specific T cell responses. However, the effect of SIT on the expression of various co‐signalling molecules has not been clarified.

Objective We sought to determine whether SIT might affect the expression of three co‐inhibitory molecules, programmed death (PD)‐1, B7‐H1 and B and T lymphocyte attenuator (BTLA), in Japanese cedar pollinosis (JCP).

Methods Peripheral blood mononuclear cells (PBMCs) were isolated from JCP patients who had or had not received SIT. PBMC were cultured in the presence or absence of Cry j 1, after which the cell surface expression of PD‐1, B7‐H1 and BTLA, as well as IL‐5 production, were determined. In addition, the effect of BTLA cross‐linking on IL‐5 production was examined.

Results After Cry j 1 stimulation, no significant differences in PD‐1 and B7‐H1 expression were observed between SIT‐treated and SIT‐untreated patients. BTLA expression was down‐regulated in untreated patients after Cry j 1 stimulation and up‐regulated in SIT‐treated patients. Up‐regulation of BTLA in SIT‐treated patients was particularly apparent in a CD4⁺ T cell subset. IL‐5 production was clearly reduced among SIT‐treated patients, and the observed changes in BTLA expression correlated negatively with IL‐5 production. Moreover, immobilization of BTLA suppressed IL‐5 production in JCP patients.

Conclusion These results suggest that both IL‐5 production and down‐regulation of BTLA in response to allergen are inhibited in SIT‐treated patients with JCP. BTLA‐mediated co‐inhibition of IL‐5 production may contribute to the regulation of allergen‐specific T cell responses in patients receiving immunotherapy.