Multiple populations of MAIT cells identified by mass cytometry and single-cell transcriptome studies (#62)
MAIT cells are a population of MR1-restricted T cells expressing a semi-invariant TCR. Previous studies showed a highly oligoclonal population of cells with limited numbers of TCR Vβ chains, indicating a strong selection pressure on TCR heterodimers by antigen recognition. Mass cytometry studies showed a heterogeneous functional capacity when six different cytokines were investigated. Whether MAIT cell distribute in different populations according to surface markers or gene expression remains to be investigated.
We performed mass cytometry analysis of MAIT cells from peripheral blood of patients with active tuberculosis, latent infection with M. tuberculosis and healthy individuals. Cells were stimulated with M. tuberculosis-infected MR1-positive APC and analysed 24 hours later with a panel of 20 monoclonal antibodies. MAIT cells were distributed in 12 distinct populations as indicated by t-SNE analysis. Each cell population was present in the three groups of donors at different levels, suggesting a skewed representation according to disease state.
The functional capacity of MAIT cells was also investigated by singe-cell transcriptome studies. T cells were purified from peripheral blood and stimulated with E. coli-infected MR1-positive APC. Activated MAIT cells were sorted and compared to non-stimulated cells. Transcriptome analysis was performed on 44 activated and 46 not-activated cells. Non-supervised clustering distributed cell populations into 2 main groups in both activated and non-stimulated cells. The physiological implications of the transcriptome differences will be discussed.