Distinct characteristics of seasonal (Bet v 1) vs. perennial (Der p 1/Der p 2) allergen-specific CD4+ T cell responses

• Published in: Clinical and experimental allergy 2011-02, Vol.41 (2), p.192-203
• Main Authors: Wambre, E., Bonvalet, M., Bodo, V. B., Maillère, B., Leclert, G., Moussu, H., Von Hofe, E., Louise, A., Balazuc, A.-M., Ebo, D., Hoarau, C., Garcia, G., Van Overtvelt, L., Moingeon, P.
• Format: Article
• Language: English
• Subjects: allergens; Antigens, Dermatophagoides - immunology; Antigens, Plant - immunology; Arthropod Proteins; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Cysteine Endopeptidases; Cytokines - biosynthesis; Cytokines - genetics; Dermatophagoides pteronyssinus; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histocompatibility Antigens Class II - immunology; Humans; immunotherapy; MHC class II tetramers; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis, Allergic, Perennial - immunology; Rhinitis, Allergic, Seasonal - immunology; Seasons; T cell polarization; tolerance
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2010.03641.x

Cite this as: E. Wambre, M. Bonvalet,V. B. Bodo, B. Maille`re, G. Leclert,H. Moussu, E. Von Hofe, A. Louise,A.‐M. Balazuc, D. Ebo, C. Hoarau,G. Garcia, L. Van Overtvelt and P. Moingeon, Clinical & Experimental Allergy, 2011 (41) 192–203. Summary Background A better understanding of allergen‐specific CD4+ T cell responses is needed to help improving immunological therapies. Objective To compare CD4+ T cell responses against seasonal (Bet v 1) and perennial (Der p 1, Der p 2) allergens. Methods Major histocompatibility complex class II peptide tetramers were engineered to monitor allergen‐specific T cell responses. After in vitro expansion, tetramer+ cells were tested for surface markers using cytofluorometry. Cytokine gene expression and production were assessed using quantitative PCR and cytokine surface capture assays, respectively. Results Tetramer+ cells were detected in 19 patients allergic to house dust mites (HDM), seven allergic to birch pollen, 13 allergic to both and nine non‐allergics with either an HLA‐DRB1*0101, *0301, *1501 or an HLA‐DPB1*0401 background. High‐avidity T cells are elicited against the immunodominant Bet v 1141−155 epitope, whereas broader low‐avidity T cell responses are induced against Der p 116−30,110−124,171−185 and Der p 226−40,107−121 epitopes. Responses against Bet v 1 involve effector (CDL62 low, CCR7 low) or central (CD62L+, CCR7+) memory cells in allergic and non‐allergic individuals, respectively, whereas central memory cells are mostly detected against mite allergens. In non‐allergics, both mite and Bet v 1‐specific T cells produce IFN‐γ and IL‐10. In contrast to Bet v 1‐driven Th2 responses, mite allergens induce highly polymorphic responses in allergics, including Th1, Th2/Th17 or mixed Th1/Th2 profiles. Mite‐specific T cell frequencies in the blood remain in the range of 1–6 × 10−4 CD4+ T cells throughout the year. Conclusion Different memory CD4+ T cell responses are elicited in the context of chronic vs. seasonal stimulation with the allergen(s). The heterogeneity in the patterns of CD4+ T cell responses observed in patients allergic to HDMs should be taken into account for specific immunotherapy.