Heterogeneity Of Specific CD4+ T Cell Responses To Peanut Allergic Components: Prospects For Specific Immunotherapy

RationalePeanut allergy is one of the most serious hypersensitivity reactions to foods in terms of persistence and severity. Conventional Specific Immunotherapy using crude peanut extract is not a recommended treatment. There is therefore an urgent need to develop a safe, disease-modifying treatment for individuals with peanut allergy. This requires details characterization of immune response to allergic components of peanut to develop suitable immunotherapeutic strategies.MethodsWe combined a CD154-based assay and a single-cell transcriptomes analysis to assess ex vivo and at a single cell level the specific CD4+ T cell responses to each peanut allergic components (Ara h) in adults with or without peanut allergy.ResultsPathogenic responses (Th2 response) were specifically associated with short life terminally differentiated allergen-specific CD4+ T cells, which dominate in allergic subjects but are absent in non-allergic subjects. Protective responses in non-atopic individuals were associated with peanut-specific TH1/TH17 cell responses. Within the peanut allergic group, we observed inter-individual variations of the specific immune response to each peanut allergic component. No direct linkage between CD4+ T cell response and IgE responses against each individual peanut allergic component.ConclusionsAbility to identify immunogenicity and type of response elicited by each peanut allergic component appears to be critical to future success in vaccine development against peanut allergy. Understanding the type of cellular response and the role of genetic restriction may allow to target immune response to critical peanut allergen and to uncover the optimal type of cellular immune response necessary for protection. RationalePeanut allergy is one of the most serious hypersensitivity reactions to foods in terms of persistence and severity. Conventional Specific Immunotherapy using crude peanut extract is not a recommended treatment. There is therefore an urgent need to develop a safe, disease-modifying treatment for individuals with peanut allergy. This requires details characterization of immune response to allergic components of peanut to develop suitable immunotherapeutic strategies. Peanut allergy is one of the most serious hypersensitivity reactions to foods in terms of persistence and severity. Conventional Specific Immunotherapy using crude peanut extract is not a recommended treatment. There is therefore an urgent need to develop a safe, disease-modifying treatment for individuals with peanut allergy. This requires details characterization of immune response to allergic components of peanut to develop suitable immunotherapeutic strategies. MethodsWe combined a CD154-based assay and a single-cell transcriptomes analysis to assess ex vivo and at a single cell level the specific CD4+ T cell responses to each peanut allergic components (Ara h) in adults with or without peanut allergy. We combined a CD154-based assay and a single-cell transcriptomes analysis to assess ex vivo and at a single cell level the specific CD4+ T cell responses to each peanut allergic components (Ara h) in adults with or without peanut allergy. ResultsPathogenic responses (Th2 response) were specifically associated with short life terminally differentiated allergen-specific CD4+ T cells, which dominate in allergic subjects but are absent in non-allergic subjects. Protective responses in non-atopic individuals were associated with peanut-specific TH1/TH17 cell responses. Within the peanut allergic group, we observed inter-individual variations of the specific immune response to each peanut allergic component. No direct linkage between CD4+ T cell response and IgE responses against each individual peanut allergic component. Pathogenic responses (Th2 response) were specifically associated with short life terminally differentiated allergen-specific CD4+ T cells, which dominate in allergic subjects but are absent in non-allergic subjects. Protective responses in non-atopic individuals were associated with peanut-specific TH1/TH17 cell responses. Within the peanut allergic group, we observed inter-individual variations of the specific immune response to each peanut allergic component. No direct linkage between CD4+ T cell response and IgE responses against each individual peanut allergic component. ConclusionsAbility to identify immunogenicity and type of response elicited by each peanut allergic component appears to be critical to future success in vaccine development against peanut allergy. Understanding the type of cellular response and the role of genetic restriction may allow to target immune response to critical peanut allergen and to uncover the optimal type of cellular immune response necessary for protection. Ability to identify immunogenicity and type of response elicited by each peanut allergic component appears to be critical to future success in vaccine development against peanut allergy. Understanding the type of cellular response and the role of genetic restriction may allow to target immune response to critical peanut allergen and to uncover the optimal type of cellular immune response necessary for protection.