Thymus-resident memory CD8+ T cells mediate local immunity.

The thymus is a primary lymphoid organ responsible for production and selection of T cells. Nonetheless, mature T cells and in particular activated T cells can reenter the thymus. Here, we identified memory CD8(+) T cells specific for lymphocytic choriomeningitis virus or vaccinia virus in the thymus of mice long-time after the infection. CD8(+) T cells were mainly located in the thymic medulla, but also in the cortical areas. Interestingly, virus-specific memory CD8(+) T cells in the thymus expressed the cell surface markers CD69 and CD103 that are characteristic of tissue-resident memory T cells in a time-dependent manner. Kinetic analyses and selective depletion of peripheral CD8(+) T cells by antibodies further revealed that thymic virus-specific memory CD8(+) T cells did not belong to the circulating pool of lymphocytes. Finally, we demonstrate that these thymus-resident virus-specific memory CD8(+) T cells efficiently mounted a secondary proliferative response, exhibited immediate effector functions and were able to protect the thymus from lymphocytic choriomeningitis virus reinfection. In conclusion, the present study not only describes for the first time virus-specific memory CD8(+) T cells with characteristics of tissue-resident memory T (T(RM)) cells in a primary lymphoid organ but also extends our knowledge about local T-cell immunity in the thymus.

Human monocytes downregulate innate response receptors following exposure to the microbial metabolite n-butyrate.

INTRODUCTION: Hyporesponsiveness of human lamina propria immune cells to microbial and nutritional antigens represents one important feature of intestinal homeostasis. It is at least partially mediated by low expression of the innate response receptors CD11b, CD14, CD16 as well as the cystine-glutamate transporter xCT on these cells. Milieu-specific mechanisms leading to the down-regulation of these receptors on circulating monocytes, the precursor cells of resident macrophages, are mostly unknown. METHODS: Here, we addressed the question whether the short chain fatty acid n-butyrate, a fermentation product of the mammalian gut microbiota exhibiting histone deacetylase inhibitory activity, is able to modulate expression of these receptors in human circulating monocytes. RESULTS: Exposure to n-butyrate resulted in the downregulation of CD11b, CD14, as well as CD16 surface expression on circulating monocytes. XCT transcript levels in circulating monocytes were also reduced following exposure to n-butyrate. Importantly, treatment resulted in the downregulation of protein and gene expression of the transcription factor PU.1, which was shown to be at least partially required for the expression of CD16 in circulating monocytes. PU.1 expression in resident macrophages in situ was observed to be substantially lower in healthy when compared to inflamed colonic mucosa. CONCLUSIONS: In summary, the intestinal microbiota may support symbiosis with the human host organism by n-butyrate mediated downregulation of protein and gene expression of innate response receptors as well as xCT on circulating monocytes following recruitment to the lamina propria. Downregulation of CD16 gene expression may at least partially be caused at the transcriptional level by the n-butyrate mediated decrease in expression of the transcription factor PU.1 in circulating monocytes.