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The mechanisms shaping the repertoire of CD4 + Foxp3 + regulatory T cells

2017; Wiley; Volume: 153; Issue: 3 Linguagem: Inglês

10.1111/imm.12859

1365-2567

Piotr Kraj, Leszek Ignatowicz,

Immunotherapy and Immune Responses

Summary Regulatory T (Treg) cells expressing Foxp3 transcription factor control homeostasis of the immune system, antigenic responses to commensal and pathogenic microbiota, and immune responses to self and tumour antigens. The Treg cells differentiate in the thymus, along with conventional CD 4 + T cells, in processes of positive and negative selection. Another class of Treg cells is generated in peripheral tissues by inducing Foxp3 expression in conventional CD 4 + T cells in response to antigenic stimulation. Both thymic and peripheral generation of Treg cells depends on recognition of peptide/ MHC ligands by the T ‐cell receptors ( TCR ) expressed on thymic Treg precursors or peripheral conventional CD 4 + T cells. This review surveys reports describing how thymus T reg cell generation depends on the selecting peptide/ MHC ligands and how this process impacts the TCR repertoire expressed by Treg cells. We also describe how Treg cells depend on sustained signalling through the TCR and how they are further regulated by Foxp3 enhancer sequences. Finally, we review the impact of microbiota‐derived antigens on the maintenance and functionality of the peripheral pool of Treg cells.