Allergen immunotherapy (AIT) is an effective treatment for allergic rhinitis, although a substantial proportion of the patients is refractory. We aimed to elucidate the mechanisms underlying the effectiveness of AIT. A 2-year clinical study was performed in adult patients with Japanese cedar pollinosis with sublingual administration of cedar pollen extract. After dividing high-responder (HR) patients with improved severity scores and non-responder (NR) patients with unchanged or exacerbated symptoms, differences in HR and NR patients were evaluated by analyzing peripheral blood cellular, serum, and genetic profiles before and after the AIT. This treatment was highly effective for rhinitis symptoms, though unimproved clinical responses were seen in ～30% of the treated patients. Serum cytokine bead array analysis failed to distinguish NR from HR patients, though cluster analysis of the serum parameters revealed a positive correlation between Th1/Th2 cytokines in HR patients before and after the AIT. In the expression of a taste receptor in CD4+ T cells, a copy number variation-related difference was observed between HR and NR patients. Through the pathway analysis of CD4+ T cell-expressing genes, an apoptosis pathway was implicated in the efficacy of AIT. CD4+ T cell is a predominant target of AIT to exhibit its efficacy on allergic rhinitis.