The lineage decisions of helper T cells (original) (raw)

• Abbas, A. K., Murphy, K. M. & Sher, A. Functional diversity of helper T lymphocytes. Nature 383, 787–793 (1996).
  Article CAS PubMed Google Scholar
• Ho, I. C. & Glimcher, L. H. Transcription: tantalizing times for T cells. Cell 109, S109–S120 (2002).
  Article CAS PubMed Google Scholar
• Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A. & Coffman, R. L. Two types of murine helper T-cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348–2357 (1986).
  CAS PubMed Google Scholar
• Szabo, S. J. et al. Distinct effects of T-bet in TH1-lineage commitment and IFN-γ production in CD4 and CD8 T cells. Science 295, 338–342 (2002).
  Article CAS PubMed Google Scholar
• Szabo, S. J. et al. A novel transcription factor, T-bet, directs TH1-lineage commitment. Cell 100, 655–669 (2000). This study reported the cloning and characterization of T-bet, which is a key regulator of T helper 1 (T H 1)-lineage commitment.
  Article CAS PubMed Google Scholar
• Mullen, A. C. et al. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292, 1907–1910 (2001).
  Article CAS PubMed Google Scholar
• Mullen, A. C. et al. Hlx is induced by and genetically interacts with T-bet to promote heritable TH1 gene induction. Nature Immunol. 3, 652–658 (2002).
  Article CAS Google Scholar
• Ouyang, W. et al. Stat6-independent GATA-3 autoactivation directs IL-4-independent TH2 development and commitment. Immunity 12, 27–37 (2000). This study showed that GATA3 might act independently of STAT6 and that GATA3 induces chromatin remodelling of the IL-4 locus.
  Article CAS PubMed Google Scholar
• Ouyang, W. et al. Inhibition of TH1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity 9, 745–755 (1998).
  Article CAS PubMed Google Scholar
• Zheng, W. & Flavell, R. A. The transcription factor GATA-3 is necessary and sufficient for TH2 cytokine gene expression in CD4 T cells. Cell 89, 587–596 (1997).
  Article CAS PubMed Google Scholar
• Zhang, D. H., Cohn, L., Ray, P., Bottomly, K. & Ray, A. Transcription factor GATA-3 is differentially expressed in murine TH1 and TH2 cells and controls TH2-specific expression of the interleukin-5 gene. J. Biol. Chem. 272, 21597–21603 (1997). References 10 and 11 were the first studies to implicate GATA3 as a T H 2-cell-specific transcription factor.
  Article CAS PubMed Google Scholar
• Lee, H. J. et al. GATA-3 induces T helper cell type 2 (TH2) cytokine expression and chromatin remodeling in committed TH1 cells. J. Exp. Med. 192, 105–115 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, G. R., Fields, P. E. & Flavell, R. A. Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level. Immunity 14, 447–459 (2001). This study defined the regulatory elements of the IL-4 locus that mediate GATA3-dependent chromatin induction.
  Article CAS PubMed Google Scholar
• Ferber, I. A. et al. GATA-3 significantly downregulates IFN-γ production from developing TH1 cells in addition to inducing IL-4 and IL-5 levels. Clin. Immunol. 91, 134–144 (1999).
  Article CAS PubMed Google Scholar
• Hsieh, C. S., Heimberger, A. B., Gold, J. S., O'Garra, A. & Murphy, K. M. Differential regulation of T helper phenotype development by interleukins 4 and 10 in an αβ T-cell-receptor transgenic system. Proc. Natl Acad. Sci. USA 89, 6065–6069 (1992).
  Article CAS PubMed PubMed Central Google Scholar
• Seder, R. A., Paul, W. E., Davis, M. M. & Fazekas de St Groth, B. The presence of interleukin-4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T-cell-receptor-transgenic mice. J. Exp. Med. 176, 1091–1098 (1992).
  Article CAS PubMed Google Scholar
• Le Gros, G., Ben-Sasson, S. Z., Seder, R., Finkelman, F. D. & Paul, W. E. Generation of interleukin-4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J. Exp. Med. 172, 921–929 (1990).
  Article CAS PubMed Google Scholar
• Swain, S. L., Weinberg, A. D., English, M. & Huston, G. IL-4 directs the development of TH2-like helper effectors. J. Immunol. 145, 3796–3806 (1990).
  CAS PubMed Google Scholar
• Kaplan, M. H., Schindler, U., Smiley, S. T. & Grusby, M. J. Stat6 is required for mediating responses to IL-4 and for development of TH2 cells. Immunity 4, 313–319 (1996).
  Article CAS PubMed Google Scholar
• Shimoda, K. et al. Lack of IL-4-induced TH2 response and IgE class switching in mice with disrupted Stat6 gene. Nature 380, 630–633 (1996).
  Article CAS PubMed Google Scholar
• Takeda, K. et al. Essential role of Stat6 in IL-4 signalling. Nature 380, 627–630 (1996).
  Article CAS PubMed Google Scholar
• Ho, I. C., Hodge, M. R., Rooney, J. W. & Glimcher, L. H. The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85, 973–983 (1996). This study was the first to identify c-MAF as a T H 2-cell-specific transcription factor.
  Article CAS PubMed Google Scholar
• Ho, I. C., Lo, D. & Glimcher, L. H. c-maf promotes T helper cell type 2 (TH2) and attenuates TH1 differentiation by both interleukin-4-dependent and -independent mechanisms. J. Exp. Med. 188, 1859–1866 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Kim, J. I., Ho, I. C., Grusby, M. J. & Glimcher, L. H. The transcription factor c-Maf controls the production of interleukin-4 but not other TH2 cytokines. Immunity 10, 745–751 (1999).
  Article CAS PubMed Google Scholar
• Hendriks, R. W. et al. Expression of the transcription factor GATA-3 is required for the development of the earliest T-cell progenitors and correlates with stages of cellular proliferation in the thymus. Eur. J. Immunol. 29, 1912–1918 (1999).
  Article CAS PubMed Google Scholar
• Pandolfi, P. P. et al. Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal-liver haematopoiesis. Nature Genet. 11, 40–44 (1995).
  Article CAS PubMed Google Scholar
• Ting, C. N., Olson, M. C., Barton, K. P. & Leiden, J. M. Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 384, 474–478 (1996).
  Article CAS PubMed Google Scholar
• Ranganath, S. et al. GATA-3-dependent enhancer activity in IL-4 gene regulation. J. Immunol. 161, 3822–3826 (1998).
  CAS PubMed Google Scholar
• Takemoto, N. et al. Cutting edge: chromatin remodeling at the IL-4/IL-13 intergenic regulatory region for TH2-specific cytokine gene cluster. J. Immunol. 165, 6687–6691 (2000).
  Article CAS PubMed Google Scholar
• Zhang, D. H. et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 11, 473–482 (1999).
  Article CAS PubMed Google Scholar
• Finotto, S. et al. Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression. J. Exp. Med. 193, 1247–1260 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Kimura, M. et al. Regulation of TH2-cell differentiation by mel-18, a mammalian polycomb-group gene. Immunity 15, 275–287 (2001).
  Article CAS PubMed Google Scholar
• Francis, N. J. & Kingston, R. E. Mechanisms of transcriptional memory. Nature Rev. Mol. Cell. Biol. 2, 409–421 (2001).
  Article CAS Google Scholar
• Zhou, M. et al. Friend of GATA-1 represses GATA-3-dependent activity in CD4+ T cells. J. Exp. Med. 194, 1461–1471 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Kurata, H. et al. Friend of GATA is expressed in naive TH cells and functions as a repressor of GATA-3-mediated TH2-cell development. J. Immunol. 168, 4538–4545 (2002).
  Article CAS PubMed Google Scholar
• Miaw, S. C., Choi, A., Yu, E., Kishikawa, H. & Ho, I. C. ROG, repressor of GATA, regulates the expression of cytokine genes. Immunity 12, 323–333 (2000).
  Article CAS PubMed Google Scholar
• Afkarian, M. et al. T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nature Immunol. 3, 549–557 (2002).
  Article CAS Google Scholar
• Finotto, S. et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295, 336–338 (2002).
  Article CAS PubMed Google Scholar
• Hentsch, B. et al. Hlx homeobox gene is essential for an inductive tissue interaction that drives expansion of embryonic liver and gut. Genes Dev. 10, 70–79 (1996).
  Article CAS PubMed Google Scholar
• Lighvani, A. A. et al. T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells. Proc. Natl Acad. Sci. USA 98, 15137–15142 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Peng, S. L., Gerth, A. J., Ranger, A. M. & Glimcher, L. H. NFATc1 and NFATc2 together control both T- and B-cell activation and differentiation. Immunity 14, 13–20 (2001).
  Article CAS PubMed Google Scholar
• Robinson, D. et al. IGIF does not drive TH1 development but synergizes with IL-12 for interferon-γ production and activates IRAK and NF-κB. Immunity 7, 571–581 (1997).
  Article CAS PubMed Google Scholar
• Yang, J., Murphy, T. L., Ouyang, W. & Murphy, K. M. Induction of interferon-γ production in TH1 CD4+ T cells: evidence for two distinct pathways for promoter activation. Eur. J. Immunol. 29, 548–555 (1999).
  Article CAS PubMed Google Scholar
• Neighbors, M. et al. A critical role for interleukin-18 in primary and memory effector responses to Listeria monocytogenes that extends beyond its effects on interferon-γ production. J. Exp. Med. 194, 343–354 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Takeda, K. et al. Defective NK-cell activity and TH1 response in IL-18-deficient mice. Immunity 8, 383–390 (1998).
  Article CAS PubMed Google Scholar
• Yang, J., Zhu, H., Murphy, T. L., Ouyang, W. & Murphy, K. M. IL-18-stimulated GADD45β required in cytokine-induced, but not TCR-induced, IFN-γ production. Nature Immunol. 2, 157–164 (2001).
  Article CAS Google Scholar
• Lu, B. et al. GADD45γ mediates the activation of the p38 and JNK MAP kinase pathways and cytokine production in effector TH1 cells. Immunity 14, 583–590 (2001).
  Article CAS PubMed Google Scholar
• Rincon, M. et al. Interferon-γ expression by TH1 effector T cells mediated by the p38 MAP kinase signaling pathway. EMBO J. 17, 2817–2829 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Dong, C., Davis, R. J. & Flavell, R. A. MAP kinases in the immune response. Annu. Rev. Immunol. 20, 55–72 (2002).
  Article CAS PubMed Google Scholar
• Lertmemongkolchai, G., Cai, G., Hunter, C. A. & Bancroft, G. J. Bystander activation of CD8+ T cells contributes to the rapid production of IFN-γ in response to bacterial pathogens. J. Immunol. 166, 1097–1105 (2001).
  Article CAS PubMed Google Scholar
• Yap, G., Pesin, M. & Sher, A. Cutting edge: IL-12 is required for the maintenance of IFN-γ production in T cells mediating chronic resistance to the intracellular pathogen, Toxoplasma gondii. J. Immunol. 165, 628–631 (2000).
  Article CAS PubMed Google Scholar
• Park, A. Y., Hondowicz, B. D. & Scott, P. IL-12 is required to maintain a TH1 response during Leishmania major infection. J. Immunol. 165, 896–902 (2000).
  Article CAS PubMed Google Scholar
• Stobie, L. et al. The role of antigen and IL-12 in sustaining TH1 memory cells in vivo: IL-12 is required to maintain memory/effector TH1 cells sufficient to mediate protection to an infectious parasite challenge. Proc. Natl Acad. Sci. USA 97, 8427–8432 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Kinjo, Y. et al. Contribution of IL-18 to TH1 response and host defense against infection by Mycobacterium tuberculosis: a comparative study with IL-12 p40. J. Immunol. 169, 323–329 (2002).
  Article CAS PubMed Google Scholar
• Oppmann, B. et al. Novel p19 protein engages IL-12 p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13, 715–725 (2000).
  Article CAS PubMed Google Scholar
• Parham, C. et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R. J. Immunol. 168, 5699–5708 (2002).
  Article CAS PubMed Google Scholar
• Belladonna, M. L. et al. IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cells. J. Immunol. 168, 5448–5454 (2002).
  Article CAS PubMed Google Scholar
• Pflanz, S. et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity 16, 779–790 (2002).
  Article CAS PubMed Google Scholar
• Devergne, O. et al. A novel interleukin-12 p40-related protein induced by latent Epstein–Barr virus infection in B lymphocytes. J. Virol. 70, 1143–1153 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Chen, Q. et al. Development of TH1-type immune responses requires the type I cytokine receptor TCCR. Nature 407, 916–920 (2000).
  Article CAS PubMed Google Scholar
• Yoshida, H. et al. WSX-1 is required for the initiation of TH1 responses and resistance to L. major infection. Immunity 15, 569–578 (2001).
  Article CAS PubMed Google Scholar
• Robinson, D. S. & O'Garra, A. Further checkpoints in TH1 development. Immunity 16, 755–758 (2002).
  Article CAS PubMed Google Scholar
• Huang, H. & Paul, W. E. Impaired interleukin-4 signaling in T helper type 1 cells. J. Exp. Med. 187, 1305–1313 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Szabo, S. J., Dighe, A. S., Gubler, U. & Murphy, K. M. Regulation of the interleukin (IL)-12R β2-subunit expression in developing T helper 1 (TH1) and TH2 cells. J. Exp. Med. 185, 817–824 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Kurata, H., Lee, H. J., O'Garra, A. & Arai, N. Ectopic expression of activated Stat6 induces the expression of TH2-specific cytokines and transcription factors in developing TH1 cells. Immunity 11, 677–688 (1999).
  Article CAS PubMed Google Scholar
• Zhu, J. et al. Growth factor independent-1 induced by IL-4 regulates TH2-cell proliferation. Immunity 16, 733–744 (2002). This study identified GFI1 as a downstream mediator of STAT6 signal transduction. It provides a basis for how IL-4 can induce the proliferation of T H 2 cells selectively.
  Article CAS PubMed Google Scholar
• Farrar, J. D. et al. An instructive component in T helper cell type 2 (TH2) development mediated by GATA-3. J. Exp. Med. 193, 643–650 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Finkelman, F. D. et al. Stat6 regulation of in vivo IL-4 responses. J. Immunol. 164, 2303–2310 (2000).
• Jankovic, D. et al. Single-cell analysis reveals that IL-4 receptor/Stat6 signaling is not required for the in vivo or in vitro development of CD4+ lymphocytes with a TH2 cytokine profile. J. Immunol. 164, 3047–3055 (2000).
  Article CAS PubMed Google Scholar
• Rodriguez-Palmero, M., Hara, T., Thumbs, A. & Hunig, T. Triggering of T-cell proliferation through CD28 induces GATA-3 and promotes T helper type 2 differentiation in vitro and in vivo. Eur. J. Immunol. 29, 3914–3924 (1999).
  Article CAS PubMed Google Scholar
• Das, J. et al. A critical role for NF-κB in GATA3 expression and TH2 differentiation in allergic airway inflammation. Nature Immunol. 2, 45–50 (2001).
  Article CAS Google Scholar
• Ghosh, P., Tan, T. H., Rice, N. R., Sica, A. & Young, H. A. The interleukin-2 CD28-responsive complex contains at least three members of the NF-κB family: c-Rel, p50 and p65. Proc. Natl Acad. Sci. USA 90, 1696–1700 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Rissoan, M. C. et al. Reciprocal control of T-helper-cell and dendritic-cell differentiation. Science 283, 1183–1186 (1999).
  Article CAS PubMed Google Scholar
• Liu, Y. J., Kanzler, H., Soumelis, V. & Gilliet, M. Dendritic-cell lineage, plasticity and cross-regulation. Nature Immunol. 2, 585–589 (2001).
  Article CAS Google Scholar
• Greenwald, R. J., Latchman, Y. E. & Sharpe, A. H. Negative co-receptors on lymphocytes. Curr. Opin. Immunol. 14, 391–396 (2002).
  Article CAS PubMed Google Scholar
• Salomon, B. & Bluestone, J. A. LFA-1 interaction with ICAM-1 and ICAM-2 regulates TH2 cytokine production. J. Immunol. 161, 5138–5142 (1998).
  CAS PubMed Google Scholar
• Camacho, S. A. et al. A key role for ICAM-1 in generating effector cells mediating inflammatory responses. Nature Immunol. 2, 523–529 (2001).
  Article CAS Google Scholar
• Luksch, C. R. et al. Intercellular adhesion molecule-1 inhibits interleukin-4 production by naive T cells. Proc. Natl Acad. Sci. USA 96, 3023–3028 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Smits, H. H. et al. Intercellular adhesion molecule-1/LFA-1 ligation favors human TH1 development. J. Immunol. 168, 1710–1716 (2002).
  Article CAS PubMed Google Scholar
• Ben-Sasson, S. Z., Gerstel, R., Hu-Li, J. & Paul, W. E. Cell division is not a 'clock' measuring acquisition of competence to produce IFN-γ or IL-4. J. Immunol. 166, 112–120 (2001).
  Article CAS PubMed Google Scholar
• Bird, J. J. et al. Helper T-cell differentiation is controlled by the cell cycle. Immunity 9, 229–237 (1998). This study was one of the first to propose a role for cell-cycle and epigenetic effects in T H -cell differentiation.
  Article CAS PubMed Google Scholar
• Mullen, A. C. et al. Cell cycle controlling the silencing and functioning of mammalian activators. Curr. Biol. 11, 1695–1699 (2001).
  Article CAS PubMed Google Scholar
• Richter, A., Lohning, M. & Radbruch, A. Instruction for cytokine expression in T helper lymphocytes in relation to proliferation and cell-cycle progression. J. Exp. Med. 190, 1439–1450 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Laouar, Y. & Crispe, I. N. Functional flexibility in T cells: independent regulation of CD4+ T-cell proliferation and effector function in vivo. Immunity 13, 291–301 (2000).
  Article CAS PubMed Google Scholar
• Sad, S. & Mosmann, T. R. Single IL-2-secreting precursor CD4 T cell can develop into either TH1 or TH2 cytokine secretion phenotype. J. Immunol. 153, 3514–3522 (1994).
  CAS PubMed Google Scholar
• Heath, V. L. et al. Cutting edge: ectopic expression of the IL-12 receptor-β2 in developing and committed TH2 cells does not affect the production of IL-4 or induce the production of IFN-γ. J. Immunol. 164, 2861–2865 (2000).
  Article CAS PubMed Google Scholar
• Nishikomori, R. et al. Activated STAT4 has an essential role in TH1 differentiation and proliferation that is independent of its role in the maintenance of IL-12Rβ2 chain expression and signaling. J. Immunol. 169, 4388–4398 (2002).
  Article CAS PubMed Google Scholar
• Mohrs, M., Shinkai, K., Mohrs, K. & Locksley, R. M. Analysis of type-2 immunity in vivo with a bicistronic IL-4 reporter. Immunity 15, 303–311 (2001).
  Article CAS PubMed Google Scholar
• Doyle, A. M. et al. Induction of cytotoxic T lymphocyte antigen 4 (CTLA-4) restricts clonal expansion of helper T cells. J. Exp. Med. 194, 893–902 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Langenkamp, A., Messi, M., Lanzavecchia, A. & Sallusto, F. Kinetics of dendritic-cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nature Immunol. 1, 311–316 (2000).
  Article CAS Google Scholar
• Sallusto, F., Lenig, D., Forster, R., Lipp, M. & Lanzavecchia, A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401, 708–712 (1999).
  Article CAS PubMed Google Scholar
• Gorelik, L., Constant, S. & Flavell, R. A. Mechanism of transforming growth factor β-induced inhibition of T helper type 1 differentiation. J. Exp. Med. 195, 1499–1505 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Gorelik, L., Fields, P. E. & Flavell, R. A. Cutting edge: TGF-β inhibits TH-type 2 development through inhibition of GATA-3 expression. J. Immunol. 165, 4773–4777 (2000).
  Article CAS PubMed Google Scholar
• Heath, V. L., Murphy, E. E., Crain, C., Tomlinson, M. G. & O'Garra, A. TGF-β1 down-regulates TH2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression. Eur. J. Immunol. 30, 2639–2649 (2000).
  Article CAS PubMed Google Scholar
• Neurath, M. F. et al. The transcription factor T-bet regulates mucosal T-cell activation in experimental colitis and Crohn's disease. J. Exp. Med. 195, 1129–1143 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Grogan, J. L. et al. Early transcription and silencing of cytokine genes underlie polarization of T-helper cell subsets. Immunity 14, 205–215 (2001). This study was one of the first to show that gene silencing mediated by trans -postioning of loci to heterochromatin might 'lock-in' states of T H -cell differentiation.
  Article CAS PubMed Google Scholar
• Kamogawa, Y., Minasi, L. A., Carding, S. R., Bottomly, K. & Flavell, R. A. The relationship of IL-4- and IFN-γ-producing T cells studied by lineage ablation of IL-4-producing cells. Cell 75, 985–995 (1993).
  Article CAS PubMed Google Scholar
• Avni, O. et al. TH-cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes. Nature Immunol. 3, 643–651 (2002).
  Article CAS Google Scholar
• Fields, P. E., Kim, S. T. & Flavell, R. A. Cutting edge: changes in histone acetylation at the IL-4 and IFN-γ loci accompany TH1/TH2 differentiation. J. Immunol. 169, 647–650 (2002).
  Article CAS PubMed Google Scholar
• Hutchins, A. S. et al. Gene silencing quantitatively controls the function of a developmental _trans_-activator. Mol. Cell 10, 81–91 (2002).
  Article CAS PubMed Google Scholar
• Agarwal, S. & Rao, A. Modulation of chromatin structure regulates cytokine gene expression during T-cell differentiation. Immunity 9, 765–775 (1998).
  Article CAS PubMed Google Scholar
• Agarwal, S., Avni, O. & Rao, A. Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo. Immunity 12, 643–652 (2000).
  Article CAS PubMed Google Scholar
• Richards, E. J. & Elgin, S. C. R. Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects. Cell 108, 489–500 (2002).
  Article CAS PubMed Google Scholar
• Ng, H. H. et al. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nature Genet. 23, 58–61 (1999).
  Article CAS PubMed Google Scholar
• Nan, X. et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393, 386–389 (1998).
  Article CAS PubMed Google Scholar
• Jones, P. L. et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nature Genet. 19, 187–191 (1998).
  Article CAS PubMed Google Scholar
• Jackson, J. P., Lindroth, A. M., Cao, X. & Jacobsen, S. E. Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature 416, 556–560 (2002).
  Article CAS PubMed Google Scholar
• Jeddeloh, J. A., Stokes, T. L. & Richards, E. J. Maintenance of genomic methylation requires a SWI2/SNF2-like protein. Nature Genet. 22, 94–97 (1999).
  Article CAS PubMed Google Scholar
• Dennis, K., Fan, T., Geiman, T., Yan, Q. & Muegge, K. Lsh, a member of the SNF2 family, is required for genome-wide methylation. Genes Dev. 15, 2940–2944 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074–1080 (2001).
  Article CAS PubMed Google Scholar
• Lee, D. U., Agarwal, S. & Rao, A. TH2-lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4. Immunity 16, 649–660 (2002).
  Article CAS PubMed Google Scholar
• Lee, P. P. et al. A critical role for Dnmt1 and DNA methylation in T-cell development, function and survival. Immunity 15, 763–774 (2001).
  Article CAS PubMed Google Scholar
• Loots, G. G. et al. Identification of a coordinate regulator of interleukins 4, 13 and 5 by cross-species sequence comparisons. Science 288, 136–140 (2000).
  Article CAS PubMed Google Scholar
• Mohrs, M. et al. Deletion of a coordinate regulator of type-2 cytokine expression in mice. Nature Immunol. 2, 842–847 (2001).
  Article CAS Google Scholar
• Solymar, D. C., Agarwal, S., Bassing, C. H., Alt, F. W. & Rao, A. A 3′ enhancer in the IL-4 gene regulates cytokine production by TH2 cells and mast cells. Immunity 17, 41–50 (2002).
  Article CAS PubMed Google Scholar
• Cirillo, L. A. et al. Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4. Mol. Cell 9, 279–289 (2002).
  Article CAS PubMed Google Scholar
• Zhang, D. H., Yang, L. & Ray, A. Differential responsiveness of the IL-5 and IL-4 genes to transcription factor GATA-3. J. Immunol. 161, 3817–3821 (1998).
  CAS PubMed Google Scholar
• Takemoto, N., Arai, K. & Miyatake, S. Cutting edge: the differential involvement of the N-finger of GATA-3 in chromatin remodeling and transactivation during TH2 development. J. Immunol. 169, 4103–4107 (2002).
  Article CAS PubMed Google Scholar
• Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6–21 (2002).
  Article CAS PubMed Google Scholar
• Hsieh, C. S. et al. Development of TH1 CD4+ T cells through IL-12 produced by _Listeria_-induced macrophages. Science 260, 547–549 (1993).
  Article CAS PubMed Google Scholar
• Murphy, K. M. et al. Signaling and transcription in T-helper development. Annu. Rev. Immunol. 18, 451–494 (2000).
  Article CAS PubMed Google Scholar
• Stetson, D. B., Mohrs, M., Mallet-Designe, V., Teyton, L. & Locksley, R. M. Rapid expansion and IL-4 expression by _Leishmania_-specific naive helper T cells in vivo. Immunity 17, 191–200 (2002).
  Article CAS PubMed Google Scholar