Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2

Abstract

Regulatory T cells (Tregs) are indispensable for maintaining self-tolerance by suppressing conventional T cells. On the other hand, Tregs promote tumor growth by inhibiting anti-cancer immunity. In this study, we identified that Tregs increase the quorum of self-reactive CD8+ T cells required for the induction of experimental autoimmune diabetes in mice. Their major suppression mechanism is limiting available IL-2, an essential T-cell cytokine. Specifically, Tregs inhibit the formation of a previously uncharacterized subset of antigen-stimulated KLRK1+ IL7R+ (KILR) CD8+ effector T cells, which are distinct from conventional effector CD8+ T cells. KILR CD8+ T cells show a superior cell killing abilities in vivo. The administration of agonistic IL-2 immunocomplexes phenocopies the absence of Tregs, i.e., it induces KILR CD8+ T cells, promotes autoimmunity, and enhances anti-tumor responses in mice. Counterparts of KILR CD8+ T cells were found in the human blood, revealing them as a potential target for immunotherapy.

Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease

“…Evaluation of the composition of post-COVID BAL by scRNAseq revealed that macrophages dominated in all subjects, with smaller T cell, NK T cell, dendritic cell, epithelial and B cell populations also identified (Figure 1b-d and Supplementary Figure 1a-d). Each of the cell types expressed high levels of independently established marker genes (Adams et al, 2020; Cheng et al, 2021; David et al, 2021; Davies et al, 2013; Davis and Wypych, 2021; Gardell and Parker, 2017; Glass et al, 2020; Murray and Wynn, 2011; Tsyklauri et al, 2023; van Aalderen et al, 2021; Villani et al, 2017), validating our annotations (Figure 1d). The notable difference between the two phenotypes was significantly higher abundance of CD4 T cells and CD8 T cells in inflammatory PCLD (Figure 1e).…”

“…Evaluation of the composition of PCLD BAL by scRNAseq revealed that macrophages dominated in all subjects, with smaller T cell, NK T cell, dendritic cell, epithelial and B cell populations also identified (Figure 1C-E and E1A-E). Detected cell types expressed high levels of established marker genes (8)(9)(10)(15)(16)(17)(18)(19)(20)(21)(22), validating our annotation strategy (Figure 1E). The notable difference between the two phenotypes was significantly higher abundance of CD4 T cells and CD8 T cells in inflammatory PCLD (Figure 1F).…”

“…A population with low numbers of genes, which could not be annotated by automatic or manual methods and likely represents empty droplets containing ambient RNA, was removed after clustering. To validate our clustering and annotation strategy, we visualized the expression of canonical or published marker genes for each cell type using a dot plot (Adams et al, 2020; Cheng et al, 2021; David et al, 2021; Davies et al, 2013; Davis and Wypych, 2021; Gardell and Parker, 2017; Glass et al, 2020; Murray and Wynn, 2011; Tsyklauri et al, 2023; van Aalderen et al, 2021; Villani et al, 2017).…”

Czech Young Immunologists: Bound by science, united in purpose

“…The online scientific events included three online journal clubs and three discussions. In the journal clubs, PhD students from the Czech Republic presented their firstauthor papers [11][12][13]. In addition to the scientific content of these journal clubs, CYI core always initiated discussions in an informal environment, so that participants were not hesitant to pose questions and had the unique chance to discuss the whole process of preparing a manuscript with the first author.…”

Induced electric fields inhibit breast cancer growth and metastasis by modulating the immune tumor microenvironment

“…This is evident by the recruitment of cell types that suppress anti-tumor immune reactivity (i.e., are immunosuppressive) such as M2-like tumor associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and T regulatory cells (Tregs) 8,9 . The recruitment of these immunosuppressive cells reduces the effector function of CD8+ T cells [10][11][12] . This immune landscape has led some to describe breast cancer as immunologically "cold" 13 .…”