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The metabolic capacity of many cells is tightly regulated and can adapt to changes in metabolic resources according to environmental changes. Tissue-resident memory (T RM ) CD8 + T cells are one of the most abundant T cell populations and offer rapid protection against invading pathogens, especially at the epithelia. T RM cells metabolically adapt to their tissue niche, such as the intestinal epithelial barrier. In the small intestine, the types of T RM cells are intraepithelial lymphocytes (IELs), which contain high levels of cytotoxic molecules and express activation markers, suggesting a heightened state of activation. We hypothesize that the tissue environment may determine IEL activity. We show that IEL activation, in line with its semiactive status, is metabolically faster than circulating CD8 + T cells. IEL glycolysis and oxidative phosphorylation (OXPHOS) are interdependently regulated and are dependent on rapid access to metabolites from the environment. IELs are restrained by local availability of metabolites, but, especially, glucose levels determine their activity. Importantly, this enables functional control of intestinal T RM cells by metabolic means within the fragile environment of the intestinal epithelial barrier.

Non-lymphoid organs, in mice and humans, contain CD8 + tissue-resident memory T (T RM ) cells. They play important roles in tissue homoeostasis as well as defence against infections and cancer. T RM cells have common characteristics that enables their tissue residency and function. However, the wide variety of tissues, some with continually exposure to invading microbes, distinct organ structures and functions, impose tissue-specific differences on T RM cells. Upon tissue-entry, they need to adapt to local circumstances by modifying their transcriptional machinery, enabling interactions with the - often specialised - surrounding cells and available metabolites. Heterogeneity amongst T RM cells may have implications for their defence function, organ-specific autoimmunity and chronic immune disorders. Here we indicate shared and unique T RM cell features within different tissues to provide a better understanding of their function and discuss possible future research directions., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Clitocybe nebularis lectin (CNL) is a GalNAcβ1-4GlcNAc-binding lectin that exhibits an antiproliferative effect exclusively on the Jurkat leukemic T cell line by provoking homotypic aggregation and dose-dependent cell death. Cell death of Jurkat cells exhibited typical features of early apoptosis, but lacked the activation of initiating and executing caspases. None of the features of CNL-induced cell death were effectively blocked with the pan-caspase inhibitor or different cysteine peptidase inhibitors. Furthermore, CNL binding induced Jurkat cells to release the endogenous damage-associated molecular pattern molecule high-mobility group box 1 (HMGB1). A plant lectin with similar glycan-binding specificity, Wisteria floribunda agglutinin (WFA) showed less selective toxicity and induced cell death in Jurkat, Tall-104, and Hut-87 cell lines. HMGB1 release was also detected when Jurkat cells were treated with WFA. We identified the CD45 and CD43 cell surface glycoproteins on Jurkat cells as the main targets for CNL binding. However, the blockade of CD45 phosphatase activity failed to block either CNL-induced homotypic agglutination or cell death. Overall, our results indicate that CNL triggers atypical cell death selectively on Jurkat cells, suggesting the potential applicability of CNL in novel strategies for treating and/or detecting acute T cell leukemia., (© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)