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CD8+ regulatory T cells (CD8+ Tregs) are a distinct subset of T lymphocytes responsible for maintaining immune homeostasis and preventing autoimmunity by suppressing the activity of various immune cells, including effector T cells and B cells [Mahnke et al., 2013, Immunology]. While CD4+ Tregs are more extensively characterized, CD8+ Tregs represent a potent regulatory population that utilizes mechanisms such as the secretion of inhibitory cytokines (IL-10, TGF-beta) and direct cell-to-cell contact-mediated suppression [Niederlova et al., 2021, Frontiers in Immunology]. In the context of autoimmune diseases and organ transplantation, a deficiency or dysfunction in CD8+ Tregs can lead to a loss of self-tolerance and chronic inflammation [Yu et al., 2018, Journal of Immunology Research]. Conversely, in oncology, an accumulation of CD8+ Tregs within the tumor microenvironment can hinder effective anti-tumor immune responses, making them a potential target for depletion or reprogramming [Salama et al., 2012, Journal of Clinical Oncology]. Current therapeutic approaches include the use of low-dose IL-2 or anti-CD3 antibodies to expand these cells in vivo, as well as ex vivo expansion for adoptive cell therapy [Sim et al., 2014, Journal of Autoimmunity]. Understanding the specific markers and functional plasticity of CD8+ Tregs is essential for developing targeted immunotherapies that can precisely modulate the immune system without causing broad immunosuppression.
Modulation of CD8+ regulatory T cell frequency and suppressive function to restore immune tolerance or enhance anti-tumor immunity.
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