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Regulatory T (Treg) cells expressing the transcription factor Foxp3 are critical for the prevention of autoimmunity and the suppression of anti-tumor immunity. The major self-antigens recognized by Treg cells remain undefined, representing a substantial barrier to the understanding of immune regulation. Here, we have identified natural Treg cell ligands in mice. We found that two recurrent Treg cell...
The promiscuous expression of tissue-restricted antigens in the thymus, driven in part by autoimmune regulator (Aire), is critical for the protection of peripheral tissues from autoimmune attack. Aire-dependent processes are thought to promote both clonal deletion and the development of Foxp3+ regulatory T (Treg) cells, suggesting that autoimmunity associated with Aire deficiency results from two...
Although antigen recognition mediated by the T cell receptor (TCR) influences many facets of Foxp3+ regulatory T (Treg) cell biology, including development and function, the cell types that present antigen to Treg cells in vivo remain largely undefined. By tracking a clonal population of Aire-dependent, prostate-specific Treg cells in mice, we demonstrated an essential role for dendritic cells (DCs)...
Elucidating the function of tumor-infiltrating regulatory T (Treg) cells has been difficult. In this issue of Immunity, Joshi et al. (2015) demonstrate that Treg cells associated with murine lung cancers are found within tertiary lymphoid structures and actively restrain effector T cells at the tumor site.
Tolerance induction in T cells takes place in most tumors and is thought to account for tumor evasion from immune eradication. Production of the cytokine TGF-β is implicated in immunosuppression, but the cellular mechanism by which TGF-β induces T cell dysfunction remains unclear. With a transgenic model of prostate cancer, we showed that tumor development was not suppressed by the adaptive immune...
To characterize the ligand binding properties of a naive T cell repertoire capable of responding to a foreign antigen, we analyzed T cell populations from T cell receptor (TCR) β transgenic mice using a novel, single cell peptide/major histocompatibility complex (MHC) tetramer dissociation assay. The largely CD4 + CD8 -/low antigen-specific thymocyte repertoire...
The basis for T cell antigen receptor (TCR) repertoire selection upon repeated antigenic challenge is unclear. We evaluated the avidity and dissociation kinetics of peptide/major histocompatibility complex (MHC) tetramer binding to antigen-specific T lymphocytes isolated following primary or secondary immunization. The data reveal a narrowing of the secondary repertoire relative to the primary repertoire,...
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