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.
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.