Type 1 regulatory T cell (Tr1)

Type 1 regulatory T (Tr1) cells are a specialized subset of CD4+ regulatory T cells that play a pivotal role in maintaining peripheral immune tolerance and preventing autoimmunity [1, 2]. Unlike classical regulatory T cells, Tr1 cells do not constitutively express the transcription factor FOXP3 but are defined by their high secretion of the immunosuppressive cytokine interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) [1, 4]. They are typically induced in the periphery following chronic antigen stimulation in a tolerogenic environment [2, 5]. Tr1 cells exert their suppressive effects through multiple mechanisms, including the inhibition of effector T cell proliferation and the direct killing of myeloid antigen-presenting cells via granzyme B and perforin [1, 16]. In therapeutic contexts, Tr1 cells are being developed as adoptive cell therapies for conditions such as graft-versus-host disease (GvHD), Crohn's disease, and type 1 diabetes [4, 7]. Pharmacological agents like Vitamin D3, dexamethasone, and IL-10 are also used to induce or expand these cells in vivo or ex vivo [5, 13]. However, their presence in the tumor microenvironment can hinder anti-tumor immunity, presenting a challenge in cancer treatment [4, 8]. Monitoring Tr1 cells often involves the use of biomarkers such as the co-expression of CD49b and LAG-3 [1, 12].

Other names

Tr1 cellT regulatory type 1 cellIL-10-producing regulatory T cellCD4+ Foxp3- regulatory T cell

Induction of peripheral tolerance through high-level secretion of IL-10 and TGF-beta [1, 2], direct cytolysis of myeloid antigen-presenting cells via granzyme B and perforin [5, 16], and suppression of effector T cell responses through metabolic disruption and inhibitory receptor signaling [1, 16].