Food allergy affects an estimated 8% of children in the US. Oral immunotherapy (OIT) is a recently approved treatment, with outcomes ranging from sustained tolerance to food allergen to no apparent benefit. The immunological underpinnings that influence clinical outcomes of OIT still remain largely unresolved. Using single-cell RNA sequencing and paired TCRα/β sequencing, we assessed the transcriptomes of CD154+ and CD137+ peanut-reactive T helper cells from 12 peanut-allergic patients longitudinally throughout OIT. We observed expanded populations of cells expressing Th1, Th2, and Th17 signatures that further separated into six clonally distinct subsets. Four of these subsets demonstrated convergence of TCR sequences, suggesting antigen-driven T cell fate. Over the course of OIT, we observed suppression of Th2 and Th1 gene signatures in effector clonotypes but not Tfh-like clonotypes. Positive outcomes were associated with stronger suppression of Th2 signatures in Th2A-like cells, while treatment failure was associated with the expression of baseline inflammatory gene signatures that were present in Th1 and Th17 populations and unmodulated by OIT. These results demonstrate that differential clinical responses to OIT are associated both with pre-existing characteristics of peanut-reactive CD4+ T cells and with suppression of a subset of Th2 cells.
Brinda Monian, Ang A. Tu, Bert Ruiter, Duncan M. Morgan, Patrick M. Petrossian, Neal P. Smith, Todd M. Gierahn, Julia H. Ginder, Wayne G. Shreffler, J. Christopher Love