Expansion of the CD4+ effector T-cell repertoire characterizes peanut-allergic patients with heightened clinical sensitivity

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:145

Article

Ruiter, Bert^1,2  Smith, Neal P.¹  Monian, Brinda³  Tu, Ang A.³  Fleming, Elizabeth¹  Virkud, Yamini V.^1,2,4  Patil, Sarita U.^1,2,4  Whittaker, Charles A.^3,5  Love, J. Christopher³  Shreffler, Wayne G.^1,2,4 

[1] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Rio 8-409,149 13th St, Boston, MA 02129 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[4] Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02129 USA

[5] MIT, Barbara K Ostrom Bioinformat & Comp Facil 1978, Swanson Biotechnol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA

关键词: Peanut allergy;    food allergy;    clinical sensitivity;    CD4(+) T cell;    effector T cell;    regulatory T cell;    T(H)2;    CD154;    TCR beta sequencing;    RNA-Seq;   

DOI  :  10.1016/j.jaci.2019.09.033

来源: Elsevier

【 摘 要 】

Background: Individuals with peanut allergy range in clinical sensitivity: some can consume grams of peanut before experiencing any symptoms, whereas others suffer systemic reactions to 10 mg or less. Current diagnostic testing only partially predicts this clinical heterogeneity. Objective: We sought to identify characteristics of the peanut-specific CD4(+) T-cell response in peanut-allergic patients that correlate with high clinical sensitivity. Methods: We studied the T-cell receptor beta-chain (TCR beta) usage and phenotypes of peanut-activated, CD154(+) CD4(+) memory T cells using fluorescence-activated cell sorting, TCR beta sequencing, and RNA-Seq, in reactive and hyporeactive patients who were stratified by clinical sensitivity. Results: TCR beta analysis of the CD154(+) and CD154(-) fractions revealed more than 6000 complementarity determining region 3 sequences and motifs that were significantly enriched in the activated cells and 17% of the sequences were shared between peanut-allergic individuals, suggesting strong convergent selection of peanut-specific clones. These clones were more numerous among the reactive patients, and this expansion was identified within effector, but not regulatory T-cell populations. The transcriptional profile of CD154(+) T cells in the reactive group skewed toward a polarized T(H)2 effector phenotype, and expression of T(H)2 cytokines strongly correlated with peanut-specific IgE levels. There were, however, also non-T(H)2-related differences in phenotype. Furthermore, the ratio of peanut-specific clones in the effector versus regulatory T-cell compartment, which distinguished the clinical groups, was independent of specific IgE concentration. Conclusions: Expansion of the peanut-specific effector T-cell repertoire is correlated with clinical sensitivity, and this observation may be useful to inform our assessment of disease phenotype and to monitor disease longitudinally.

【 授权许可】

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