BACKGROUND Specific immunotherapy (SIT) acts by inducing a shift from T(H)2 to T(H)1 cell response on mucous membranes, reducing allergic inflammation. New genes expressed primarily in T(H)1-type cells have been found. Of these genes, signaling lymphocytic activation molecule (SLAM) promotes T-cell proliferation and IFN-gamma production. Nothing is known about its role in T(H)2-T(H)1 switch during SIT. OBJECTIVE We sought to analyze the mRNA expression of SLAM and other T(H)1-associated genes, interleukin-12 receptor beta2 (IL-12Rbeta2) and T-box expressed in T cells (T-bet), and compare them with the clinical outcome of the therapy. METHODS PBMC from 30 patients allergic to pollen undergoing SIT were collected during the therapy. Control PBMC were collected from 10 patients with allergic rhinitis not participating in SIT and from 10 nonallergic subjects. Cells were stimulated in vitro with pollen allergen extracts. SLAM, IL-12Rbeta2, and T-bet mRNA expressions were studied by real-time quantitative RT-PCR technique (Taqman). Symptom scoring and medication scoring were registered before commencement of SIT and after 1 year of the therapy. RESULTS Before the treatment, in vitro allergen-induced SLAM mRNA expression in PBMC was significantly lower in the patients with allergic rhinitis than in the healthy control subjects. After 1 year of the treatment, SLAM mRNA expression was increased in the patients undergoing SIT and was associated with IFN-gamma mRNA expression and inversely associated with the symptom improvement. At the maintenance dose, an increase in SLAM mRNA expression was associated with the clinical symptom improvement at 1 year. No changes were seen in IL-12Rbeta(2) or T-bet mRNA expressions. CONCLUSIONS SLAM mRNA expression in PBMC is modulated during the course of SIT, and an early and transient increase of SLAM mRNA expression is associated with clinical symptom improvement.