Mounting an efficient immune response to pathogens while avoiding damage to host tissues is the central task of the immune system. Emerging evidence has highlighted the contribution of the CD8(+) lineage of regulatory T cells to the maintenance of self-tolerance. Specific recognition of the MHC class Ib molecule Qa-1 complexed to peptides expressed by activated CD4(+) T cells by regulatory CD8(+) T cells triggers an inhibitory interaction that prevents autoimmune responses. Conversely, defective Qa-1-restricted CD8(+) regulatory activity can result in development of systemic autoimmune disease. Here, we review recent research into the cellular and molecular basis of these regulatory T cells, their mechanism of suppressive activity and the potential application of these insights into new treatments for autoimmune disease and cancer.
"T cells, a subpopulation of adaptive lymphocytes, play an important role in immunity to intracellular pathogens and tumors (Gattinoni et al. 2012; Klenerman and Hill 2005; Kuang et al. 2010; Lu et al. 2014). They also contribute to the regulation of pathologic processes such as autoimmune and allergic disorders (Huber et al. 2009; Kim and Cantor 2011; Loser et al. 2010; Tang et al. 2012; Visekruna et al. 2013). Naı¨ve CD8 ? "
[Show abstract][Hide abstract] ABSTRACT: It is well established that CD8(+) T cells constitute an important branch of adaptive immunity contributing to clearance of intracellular pathogens and providing long-term protection. These functions are mostly fulfilled by the best characterized subpopulation of CD8(+) T cells, the cytotoxic T lymphocytes (also called Tc1 cells), owing to their ability to kill infected cells and to secrete cytokines such as interferon-γ and tumor necrosis factor-α. However, there is growing evidence for alternative CD8(+) T cell fates influencing CD4(+) T-cell-mediated responses in the context of allergy, autoimmunity and infections. Thus, like subpopulations of CD4(+) T cells, also CD8(+) T cells under particular conditions acquire the expression of interleukin (IL)-4, IL-5, IL-9, IL-13, IL-17 or suppressive activity and thereby influence immune responses. The process of CD8(+) T-cell differentiation is dictated by antigen strength, co-stimulatory molecules and cytokines. These environmental cues induce transcription factors further specifying CD8(+) T-cell decision into Tc1, Tc2, Tc9, Tc17 or CD8(+) T regulatory fate. Here, we discuss our current understanding about functional diversity of effector CD8(+) T cells and contribution of transcription factors to this process.
Janine Gotot, Eveline Piotrowski, Martin S Otte, André P Tittel, Guo Linlin, Chen Yao, Karl Ziegelbauer, Ulf Panzer, Natalio Garbi, Christian Kurts, Friedrich Thaiss,
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