Single-cell transcriptome and T cell receptor profiling of the tuberculin skin test

Abstract

The tuberculin skin test (TST) is a cutaneous delayed hypersensitivity reaction to antigen from Mycobacterium tuberculosis (Mtb). We provide the first single cell sequencing characterisation of the human TST reaction, based on skin suction blisters induced at the site of the TST on day 2 in 31 individuals. Integrated single cell RNA and TCR sequencing showed the immune response to be dominated by T cells, with smaller populations of NK cells and myeloid cells. T cells comprised CD4, CD8, gamma/delta and NK T cells, with 50% of all T cells identified as cytotoxic and 14% as regulatory. Interferon gamma gene expression was strongest in CD8 T cells, and distinct CD4 T helper lineages could not unambiguously be identified at this time point. Amongst myeloid cells, 63% displayed antimicrobial gene expression and 28% were functionally polarised towards antigen presentation with higher levels of HLA class 2 expression. We derived and validated transcriptional signatures for cell types and cellular functions relevant to the immune landscape of the TST. These data help to improve our understanding of the immune response to Mtb and enable further exploration of bulk transcriptomic data through context-specific cellular deconvolution.