Journal ArticleDOI
The role of interleukin-2 during homeostasis and activation of the immune system.
TLDR
Interleukin-2 signals influence various lymphocyte subsets during differentiation, immune responses and homeostasis and can amplify CD8+ T cell responses or induce the expansion of the TReg cell population, thus favouring either immune stimulation or suppression.Abstract:
Interleukin-2 (IL-2) signals influence various lymphocyte subsets during differentiation, immune responses and homeostasis. As discussed in this Review, stimulation with IL-2 is crucial for the maintenance of regulatory T (T(Reg)) cells and for the differentiation of CD4(+) T cells into defined effector T cell subsets following antigen-mediated activation. For CD8(+) T cells, IL-2 signals optimize both effector T cell generation and differentiation into memory cells. IL-2 is presented in soluble form or bound to dendritic cells and the extracellular matrix. Use of IL-2 - either alone or in complex with particular neutralizing IL-2-specific antibodies - can amplify CD8(+) T cell responses or induce the expansion of the T(Reg) cell population, thus favouring either immune stimulation or suppression.read more
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Regulatory T cells in cancer immunotherapy
Atsushi Tanaka,Shimon Sakaguchi +1 more
TL;DR: It is hoped that combination of Treg-cell targeting with the activation of tumor-specific effector T cells will make the current cancer immunotherapy more effective.
Journal ArticleDOI
Interleukin-2 at the Crossroads of Effector Responses, Tolerance, and Immunotherapy
TL;DR: This review focuses on the molecular mechanisms and complex cellular actions of IL-2, its cooperative and opposing effects with other cytokines, and how both promoting and blocking the actions ofIL-2 are being utilized in clinical medicine.
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Regulatory T cells in cancer immunosuppression — implications for anticancer therapy
TL;DR: Novel insights are discussed into the roles of Treg cells in cancer, which can hopefully be used to develop Treg cell-targeted therapies and facilitate immune precision medicine.
Journal ArticleDOI
Remote control of therapeutic T cells through a small molecule-gated chimeric receptor
TL;DR: The ON-switch CAR exemplifies a simple and effective strategy to integrate cell-autonomous decision-making with exogenous, reversible user control and highlights the importance of developing optimized bio-inert, orthogonal control agents such as small molecules and light, together with their cellular cognate response components, in order to advance precision-controlled cellular therapeutics.
Journal ArticleDOI
Vaccines for established cancer: overcoming the challenges posed by immune evasion.
TL;DR: How therapeutic benefit can be maximized in patients with established cancers by using vaccines to increase the effects of standard chemotherapies, to establish and/or maintain tumour-specific T cells that are re-energized by checkpoint blockade and other therapies, and to sustain the antitumour response of adoptively transferred T cells is summarized.
References
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Journal ArticleDOI
Differentiation of Effector CD4 T Cell Populations
TL;DR: This review summarizes the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation.
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CD4+CD25+ Immunoregulatory T Cells Suppress Polyclonal T Cell Activation In Vitro by Inhibiting Interleukin 2 Production
TL;DR: Data support the concept that the CD4+CD25+ T cells in normal mice may represent a distinct lineage of “professional” suppressor cells.
Journal ArticleDOI
CTLA-4 Control over Foxp3+ Regulatory T Cell Function
Kajsa Wing,Yasushi Onishi,Yasushi Onishi,Paz Prieto-Martin,Tomoyuki Yamaguchi,Makoto Miyara,Zoltan Fehervari,Takashi Nomura,Shimon Sakaguchi,Shimon Sakaguchi +9 more
TL;DR: It is shown that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell–mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice.
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Follicular Helper CD4 T Cells (TFH)
TL;DR: This review discusses recent progress and areas of uncertainty or disagreement in the literature, and debates the developmental relationship between T(FH) cells and other CD4 T cell subsets (Th1, Th2, Th17, iTreg).
Journal ArticleDOI
Selective in vitro growth of T lymphocytes from normal human bone marrows
TL;DR: The T cells exhibited a strict growth dependence upon Phytohemagglutinin-stimulated normal human lymphocytes and were consistently negative for Epstein-Barr viral information.