Lineage commitment in the immune system: the T helper lymphocyte grows up.

By L. H. Glimcher, Kenneth M. Murphy. Genes & Development, 2000

701 citations recorded by the source corpus.

Cells of the immune system provide particularly fruitful subjects for the study of lineage commitment. Both T and B lymphocytes undergo complicated patterns of differentiation from uncommitted, nonfunctional precursor cells to highly sophisticated effector cells. The development of the helper T lymphocyte is one of the most elegant examples of this. A little over a decade ago, Mosmann and Coffman (1989) discovered that naive mouse CD4 T helper lymphocytes, upon receiving an antigenic stimulus, differentiate into two distinct subsets defined both by their function and by unique cytokine profiles. These subsets, T helper 1 (Th1) and T helper 2 (Th2) (Mosmann et al. 1986; Mosmann and Coffman 1989; Paul and Seder 1994; O’Garra 1998; Rengarajan and Glimcher 2000), are responsible for cell-mediated/inflammatory immunity and humoral responses, respectively (Fig. 1). This division of labor fits nicely with previous demonstrations that an organism tends to mount either a cell-mediated or humoral response, but not both, in response to pathogens. The function of T helper cells can largely be explained by the cytokines they secrete. Cytokines (or lymphokines) are small hormone-like polypeptides that have pleiotrophic biological activities in several cell types. Resting T cells do not transcribe cytokine genes, but they are rapidly induced upon coactivation through the T-cell receptor (TCR) and costimulatory receptors (Lenschow et al. 1996). Much progress has been made in identifying the signaling pathways and transcription factors that control Th1 and Th2 differentiation as shown schematically (Fig. 2a). This review will summarize what is currently known about the signals that regulate lineage commitment in T helper cells with a special focus on three subset-specific transcription factors, T-bet, GATA-3, and c-Maf, responsible for lineage commitment (Fig. 2b).

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/7d10d44be86b2e8a75ece4d43ff799c88cb51818

How researchers see this paper

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In Immunology

1. Dan R. Littman
2. K. Honda
3. A. O’Garra
4. D. Cua
5. Laurie H. Glimcher
6. C. Hawrylowicz
7. P. Hogan
8. Anjana Rao

Citations in the corpus

• T-Bet Expression and Failure of GATA-3 Cross-Regulation Lead to Default Production of IFN-γ by γδ T Cells1 (2002, background): “The balance between T-bet and GATA-3 is critical for the outcome of CD4 T cell differentiation (18); however, the precise role of T-bet and GATA-3, and the relationship between these two transcription factors, in T cell differentiation are unknown.”
• Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. (2004, background): “Whether effector cells differentiate to support primarily cytotoxic, interferonγ -driven (type 1) responses or humoral, IL-4-dependent (type 2) responses depends on a variety of factors that have been reviewed elsewhere (205, 206).”
• In Vitro Generation of Interleukin 10–producing Regulatory CD4+ T Cells Is Induced by Immunosuppressive Drugs and Inhibited by T Helper Type 1 (Th1)– and Th2-inducing Cytokines (2002, background): “Key transcription factors have been associated with the differentiation of Th1 and Th2 cell subsets (47, 48).”
• Induction of intestinal Th17 cells by segmented filamentous bacteria (2009, background): “T helper type 1 (Th1) and Th2 cells control intracellular microorganisms and helminths, respectively (Abbas et al., 1996; Glimcher and Murphy, 2000), whereas the induced regulatory T (iTreg) cells suppress excessive immune responses (Gavin and Rudensky, 2003).”
• Transcriptional regulation by calcium, calcineurin, and NFAT. (2003, background): “…NFAT2 is reported to have a predominant role in at least two cellular differentiation programs in vivo: differentiation of osteoclasts from monocyte precursors (Takayanagi et al. 2002) and differentiation of Th2 cells from antigen-“naive” T cells (for review, see Glimcher and Murphy 2000).”