Signatures and Specificity of Tissue-Resident Lymphocytes Identified in Human Renal Peritumor and Tumor Tissue.

Background: Tissue-resident memory T (T) cells are known to be important for the first line of defense in mucosa-associated tissues. However, the composition, localization, effector function, and specificity of T cells in the human kidney and their relevance for renal pathology have not been investigated.

Methods: Lymphocytes derived from blood, renal peritumor samples, and tumor samples were phenotypically and functionally assessed by applying flow cytometry and highly advanced histology (multi-epitope ligand cartography) methods.

Mucosal associated invariant T cells are differentially impaired in tolerant and immunosuppressed liver transplant recipients.

Mucosal associated invariant T (MAIT-) cells represent a semi-invariant T cell population responsive to microbial vitamin B metabolite and innate cytokine stimulation, executing border tissue protection and particularly contributing to human liver immunity. The impact of immunosuppressants on MAIT cell biology alone and in context with solid organ transplantation has not been thoroughly examined. Here, we demonstrate that in vitro cytokine activation of peripheral MAIT cells from healthy individuals was impaired by glucocorticoids, whereas antigen-specific stimulation was additionally sensitive to calcineurin inhibitors.

The TL1A-DR3 Axis Selectively Drives Effector Functions in Human MAIT Cells.

Mucosal-associated invariant T (MAIT) cells are semi-invariant T cells specifically recognizing riboflavin derivatives that are synthesized by many bacteria and fungi presented by MHC class I-related MR1 molecules. Accumulating evidence, however, indicates that MAIT cell functions are inducible by cytokine stimuli in the absence of TCR ligation, identifying MAIT cells as innate sentinels in inflammatory environments. In this study, we demonstrate that death receptor 3 (DR3), a member of the TNFR superfamily, is ex vivo expressed and predominantly upregulated on the surface of human MAIT cells by innate cytokine stimulation.