Mechanisms of desensitisation in oral immunotherapy
Recent advances in our understanding of the immune changes associated with desensitisation have arisen from gene expression profiling of the peanut-reactive T cell compartment. These have included the identification of Th2A cells, also called peTh2, a pathogenic reservoir of Th2 cells elevated in allergic individuals24,26,27. Th2A are a subset of cells that are distinctive from conventional Th2 cells. This subset is terminally differentiated, lacks CD27 expression, produces very high levels of Th2 effector cytokines, and is characterised by the markers CRTH2, CD49d, CD161. Transcriptomic analysis of Th2A cells by microarray in allergic individuals (n=3 donors) revealed a unique immunological program that induces a pathogenic response to allergen. Using ex vivo pMHCII tetramer–based T cell profiling, the authors showed that this subset was reduced in frequency compared to baseline frequencies in patients who achieved desensitisation following oral immunotherapy (n=4)26.
Profiling of peanut reactive T cells using scRNAseq has shed light on modifications to the Th2A population during OIT. Suppression of the Th2 transcriptional signals in Th2A-like cells was linked to desensitisation following OIT in a study of cells from n=12 participants at 0, 13, 58 and 70 weeks21. However, it was supressed to a similar extent in both those who went on to fail a second food challenge after a period of 3 months of allergen avoidance following treatment (desensitised without SU), indicating no association with remission21. Furthermore, desensitisation was not linked to a complete elimination of these cells, which may point to a reservoir of Th2A cells, capable of expanding and contributing to a failure to achieve lasting protection.