After activation, CD4+ T cells can differentiate into different lineages of T helper (TH) cells with distinct biological functions.
Nearly 20 years ago, TH cells were first divided into two subsets: TH1 cells that produce interferon-y to support cell-mediated immunity and TH2 cells that produce interleukin-4 (IL-4) to support humoral immunity. In 2006, IL-17-expressing T cells (TH17 cells) were proposed to be a third, independent TH-cell lineage with a role in inflammatory and autoimmune diseases. This Focus brings together the latest research on how the differentiation of TH-cell subsets and regulatory T (TReg) cells is controlled and cross-regulated by various cytokines, transcription factors and epigenetic mechanisms. All of the articles in this Focus are available free to registered users until 31 July 2009.
Foreword
Decision making during the conception and career of CD4+ T cells
Steven L. Reiner
doi:10.1038/nri2490
Nature Reviews Immunology 9, 81-82 (2009)
Research Highlights
T-cell development: Stimulating company
Lucy Bird
doi:10.1038/nri2502
Nature Reviews Immunology 9, 72 (2009)
T-cell responses: Two for the price of one
Kirsty Minton
doi:10.1038/nri2495
Nature Reviews Immunology 9, 74-75 (2009)
T-cell development: CD40–CD40L crosstalk in TH17-cell differentiation
Olive Leavy
doi:10.1038/nri2499
Nature Reviews Immunology 9, 76 (2009)
Dendritic cells: Tailoring T-helper-cell responses
Sarah Allan
doi:10.1038/nri2500
Nature Reviews Immunology 9, 76 (2009)
In Brief
doi:10.1038/nri2504
Nature Reviews Immunology 9, 73 (2009)
Progress
Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage?
Jochen Huehn, Julia K. Polansky & Alf Hamann
doi:10.1038/nri2474
Nature Reviews Immunology 9, 83-89 (2009)
Regulatory T (TReg) cells are crucial for immune homeostasis, and manipulation of their suppressive functions is a possible avenue for immunotherapy. Here, the authors discuss recent advances in our understanding of how the expression of forkhead box P3 (FOXP3), a TReg-cell-specifying transcription factor, is controlled at the molecular level.
Reviews
Epigenetic control of T-helper-cell differentiation
Christopher B. Wilson, Emily Rowell & Masayuki Sekimata
doi:10.1038/nri2487
Nature Reviews Immunology 9, 91-105 (2009)
Numerous lineage-specific transcription factors have been linked with T-helper-cell subset specification. But, as discussed here, epigenetic modifications at the gene regulatory elements where these factors bind can also contribute to the regulation of T-helper-cell differentiation and function.
RUNX proteins in transcription factor networks that regulate T-cell lineage choice
Amélie Collins, Dan R. Littman & Ichiro Taniuchi
doi:10.1038/nri2489
Nature Reviews Immunology 9, 106-115 (2009)
In this Review, the authors discuss how RUNX (runt-related transcription factor) proteins and other key transcription factors work together to direct T-cell lineage choice and CD4+ T-cell differentiation.
The different faces of Notch in T-helper-cell differentiation
Derk Amsen, Andrey Antov & Richard A. Flavell
doi:10.1038/nri2488
Nature Reviews Immunology 9, 116-124 (2009)
Recent research indicates that the Notch signalling pathway is important for directing T helper (TH)-cell differentiation. In this Review, the authors discuss contrasting results showing that Notch can have a role in both TH1- and TH2-cell differentiation, and highlight how this information might help to better understand the pathology of T-cell-mediated diseases.
GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation
I-Cheng Ho, Tzong-Shyuan Tai & Sung-Yun Pai
doi:10.1038/nri2476
Nature Reviews Immunology 9, 125-135 (2009)
The transcription factor GATA-binding protein 3 (GATA3) is best known as a master regulator of T-helper-2-cell differentiation. However, as part of a network of other transcription factors, GATA3 is also important in determining cell fate at earlier stages of haematopoiesis and lymphoid-cell development.
Perspectives
OPINION
Regulation of T-helper-cell lineage development by osteopontin: the inside storyHarvey Cantor & Mari L. Shinohara
doi:10.1038/nri2460
Nature Reviews Immunology 9, 137-141 (2009)
Here, Harvey Cantor and Mari Shinohara propose that the secreted and intracellular isoforms of osteopontin differentially regulate the development of distinct T-helper-cell subsets and, consequently, adaptive immune responses to foreign and self antigens.
© 2018 Macmillan Publishers Limited, part of Springer Nature. All Rights Reserved.
