T cell clustering: CD8+ T cell clusters
predominate in COVID-MDR
To analyze the T cell compartment in more detail, we sub-clustered
CD4+ and CD8+ T cells into 4 subsets
each (Figure 3A-B, Figure S3A). Among CD8+ T cells,
the most proliferative and cytotoxic cluster IV was increased in
COVID-MDR. These cells showed strong expression of Ki67, GrzB, CD16 and
the co-stimulation/activation marker CD27. Separation of
CD8+ T cells by indication confirmed that
CD8+ COVID-MDR T cells exhibit a more cytotoxic
phenotype in comparison to MDR and DRESS (Figure S3A). All DDH showed
elevated levels of CLA- CD8+ T
cells, indicating an influx of non- resident T cells into the skin
(Figure 2E, Figure 3A-B). Regarding CD4+ T cells, no
differences were observed between the DDH samples and overall
frequencies were similar to HC.
Of note, in some CD8+ and CD4+ T
cell clusters and especially in COVID-MDR, we observed the expression of
certain myeloid markers (CD1c, CD11c, CD40, CD163) (Figure 3B). These
signals are most likely observed due to low resolution of our images and
the limits of cellular segmentation. Thus one can assume that T cells
that express myeloid markers are in spatial proximity to myeloid cells
which may be the cells that actually activate the T cells.