Changes in peanut-specific T-cell clonotype with oral immunotherapy

• Published in: Journal of allergy and clinical immunology 2015-06, Vol.135 (6), p.1636-1638.e3
• Main Authors: Bégin, Philippe, MD, MSc, FRCPC, Nadeau, Kari C., MD, PhD, FAAAAI
• Format: Article
• Language: English
• Subjects: Adolescent; Allergens - administration & dosage; Allergens - immunology; Allergies; Allergy and Immunology; Anti-Allergic Agents - therapeutic use; Antibodies, Anti-Idiotypic - therapeutic use; Antibodies, Monoclonal, Humanized - therapeutic use; Antigens; Arachis - chemistry; Arachis - immunology; Cellular Reprogramming; Child; Child, Preschool; Clone Cells; Female; Food allergies; Gene Expression; Genotype & phenotype; Humans; Hypotheses; Immunotherapy; Information theory; Lymphocytes; Male; Omalizumab; Peanut Hypersensitivity - genetics; Peanut Hypersensitivity - immunology; Peanut Hypersensitivity - pathology; Peanut Hypersensitivity - therapy; Plant Proteins - administration & dosage; Plant Proteins - immunology; Population; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; Software; Sublingual Immunotherapy; Tetanus; Th1 Cells - immunology; Th1 Cells - pathology; Th2 Cells - immunology; Th2 Cells - pathology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2015.03.010

To the Editor: Allergen-proliferation assays are widely used to determine allergen-specific changes in T-cell phenotype during immunotherapy, generally showing skewing of the pathological TH2 response toward a normal TH1 or regulatory T-cell response.1,2 Concerns have been raised, however, about the actual specificity of this approach, which often leads to the identification of very high rates of TH1 cells.3 Another question that is yet to be elucidated is whether the observed changes result from a reprogramming of existing allergen-specific clones (reeducation hypothesis) or from their replacement by different clones to determine the dominant response (replacement hypothesis). The authors found that allergen-stimulated carboxyfluorescein succinimidyl esterlo CD4+ T cells contained only 0.3% to 10.7% of Art v1-tetramer+ T cells and very low proportions of TH2 cells, suggesting an extremely high TH1 bystander proliferation.3 One hypothesis to explain this bystander proliferation would be that the bystanders represent naive T cells, which tend to proliferate despite low antigen affinity, as opposed to memory T cells, which show robust response to high-affinity antigens only.7 The naive repertoire is much more diverse than its memory counterpart (up to 108 compared with 106 clones in healthy individuals).8 When comparing immediate repeat blood draws at the "survey" level, the concordance of naive repertoire was very low (4.5% TCR overlap; R = 0.321) compared with that of the memory compartment (47.5% TCR overlap; R = 0.861) (see Fig E1 in this article's Online Repository at www.jacionline.org).