Many individuals suffer from allergies to cats, primarily caused by the protein Fel d 1, which is found in cat saliva, skin, and fur. Current treatments mainly involve pharmacotherapy that alleviates symptoms but does not cure the allergy, and while effective for mild cases, these treatments are less successful for those with moderate to severe allergies. Researchers are exploring allergen-specific immunotherapy (AIT), which aims to induce long-term immune tolerance in severe allergy cases by modifying immune responses through regulatory lymphocytes.
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A study conducted by researchers at the Luxembourg Institute of Health’s Department of Infection and Immunity focused on enhancing immune tolerance to Fel d 1 using a higher dose of the established immunomodulatory adjuvant CpG. By optimizing regulatory T- and B-cell responses, the researchers aimed to block the allergen’s effects more effectively. AIT typically involves subcutaneous injections of progressively increasing doses of allergens to build tolerance.
The study involved injecting Fel d 1 allergen combined with high doses of CpG into Fel d 1-allergic mice, both with and without AIT. The findings showed a notable increase in plasmacytoid dendritic cells at the injection site and in lymphoid organs early in the AIT process. These dendritic cells can guide the development of regulatory T cells, confirming an increase in these immune cells. Though the research indicated a rise in regulatory B cells, no measurable changes in IL-10 or TGF-β secretion were observed in live subjects, despite their known role in mediating tolerance.
Furthermore, the early phase of CpG-based AIT also triggered a swift increase in natural killer cells characterized by a TNF-α/TNFR2 profile, which could enhance regulatory T cell differentiation and activity. The researchers concluded that AIT utilizing high-dose CpG alongside endotoxin-free Fel d 1 counteracts key allergy characteristics, suggesting CpG's potential to enhance allergen-specific tolerance in cat allergy patients and potentially in other allergic conditions.
These findings are documented in the 2020 journal article by Leonard et al. titled "Comprehensive mapping of immune tolerance yields a regulatory TNF receptor 2 signature in a murine model of successful Fel d 1-specific immunotherapy using high-dose CpG adjuvant," published in Allergy.