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.