Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells.

Kaye, Jonathan; Porcelli, Steven A.; Tite, J P; Jones, Barry; Janeway, Charles A.

doi:10.1084/jem.158.3.836

Cited by 622 publications

(206 citation statements)

References 28 publications

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“…2c illustrates measurements for individual GATA-3 alleles normalized to the nuclear radius, confirming the preferential association of GATA-3 with centromeric heterochromatin in polarized Th1 but not Th2 cells (p<0.01). This preferential association persisted in long term T cell lines and clones (p<0.01, Th1 clone D5 [23] versus Th2 clone D10 [24] and Th2 line GAD [25]). The cytogenetic position of the GATA-3 locus only 9.8 Mb from the centromere of chromosome 2 (Ensemble) is likely to impose topological restrictions, underlining the significance of the differential positioning of GATA-3 in Th1 and Th2 interphase nuclei [26].…”

Section: Resultsmentioning

confidence: 87%

“…Th1 cells were moved from antibody-coated to fresh culture wells 2 h after restimulation to minimize activation-induced cell death (not shown). T cell clones D5 (Ar-5) [23] and D10 (D10.G4.1) [24] were cultured in Dulbecco's modified Eagle's medium supplemented with 10% FCS, L-glutamine, penicillin-streptomycin, nonessential amino acids, sodium pyruvate, vitamins, HEPES, and 2-ME and 20 U/ml human rIL-2 (for D5) or 25 U/ml recombinant IL-4 (for D10). PGL2 (Th1) and PL104 (Th2) clones and the Th2 anti-GAD 524-543 T cell line have been described [25,42].…”

Section: Mice and Cellsmentioning

confidence: 99%

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Nuclear repositioning marks the selective exclusion of lineage‐inappropriate transcription factor loci during T helper cell differentiation

et al. 2004

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To address how heritable patterns of gene expression are acquired during the differentiation of Th1 and Th2 cells, we analyzed the nuclear position of lineage-restricted cytokine genes and their upstream regulators by 3-dimensional fluorescence in situ hybridization. During Th1 differentiation, GATA-3 and c-maf loci, which encode upstream regulators of Th2 cytokines, were progressively repositioned to centromeric heterochromatin as defined by a c-satellite repeat probe and/or the nuclear periphery, compartments that have been associated with transcriptional repression. A third transcription factor locus, T-bet, which controls Th1-specific programs, was subject to de novo CpG methylation in a Th2 cell clone. In contrast, we did not find repositioning of the cytokine gene loci IL-2, IL-3, IL-4 or IFN-c during T helper cell differentiation. Instead, IFN-c was constitutively associated with the nuclear periphery, even when primed for expression in Th1 cells. Our results suggest that Th1/Th2 lineage commitment and differentiation involve repositioning of the regulators of cytokine expression, rather than the cytokine genes themselves.

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Section: Resultsmentioning

confidence: 87%

Section: Mice and Cellsmentioning

confidence: 99%

Nuclear repositioning marks the selective exclusion of lineage‐inappropriate transcription factor loci during T helper cell differentiation

et al. 2004

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“…Non-T cells used in this study include the murine B-cell hybridoma LK 35.2 (29), the human B-cell line Namalwa, and the human epithelial cell line HeLa. For mature TCR+ T cells, we used the human T-cell line Jurkat and the antigen-specific T-cell clones D10 and L3 (30,40). D10 is mature CD4+ CD8-helper T clone whose TCR recognizes conalbumin presented on I-Ak MHC.…”

Section: Materlils and Methodsmentioning

confidence: 99%

Elf-1 binds to a critical element in a second CD4 enhancer.

Wurster¹,

Siu²,

Leiden³

et al. 1994

Mol. Cell. Biol.

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The coordinated expression of CD4 and CD8 during T-cell development is tightly coupled with the maturation state of the T cell. Additionally, the mutually exclusive expression of these receptors in mature T cells is representative of the functional T-cell subclasses (CD4+ helper T cells versus CD8+ cytotoxic T cells). We have studied the regulation CD4 gene transcription during T-cell development in an attempt to gain an understanding of the molecular mechanisms involved in T-cell development and differentiation. Here we present the identification of a second transcriptional enhancer in the murine CD4 locus 24 kb upstream of the CD4 promoter. This enhancer is active in mature T cells and is especially active in CD4+ helper T cells. A number of nuclear proteins bind to elements in the minimal CD4 enhancer that includes consensus sites for AP-1, Spl, Gata, and Ets transcription factor families. We find that the Ets consensus site is crucial for enhancer activity and that the recently identified Ets factor, Elf-i, which is expressed at high levels in T cells and involved in the regulation of several other T-cell-specific genes, is a dominant protein in T-cell nuclear extracts that binds to this site.T-cell development involves the differentiation of functionally immature pre-T cells into mature, antigen-reactive effector cells (reviewed in reference 61). This process includes selection events in which the maturing T-cell population is depleted of self-reactive clones and enriched for those that can recognize foreign peptides bound by self-major histocompatibility complex (MHC). The development and selection of T-cell precursors occur in the thymus and are characterized by a coordinated expression of tissue-specific genes. Some of these genes encode cell surface molecules that directly promote T-cell differentiation and selection events. Understanding the molecular mechanisms responsible for the expression of these T-cellspecific genes is a window on the process of T-cell development.The CD4 glycoprotein is one of the surface molecules that is important as a receptor in the development and function of T cells (reviewed in references 39 and 46). In mature antigenspecific T cells, CD4 is expressed only on cells that have a T-cell receptor (TCR) specific for antigen associated with class II MHC molecules, while CD8, a cell surface protein functionally similar to CD4, is expressed only on T cells that recognize antigen bound to MHC class I molecules (56). The mutually exclusive expression of CD4 and CD8 on mature T cells also corresponds to T-cell function; CD4 is expressed primarily on helper T cells, while CD8 is expressed on cytotoxic T cells. CD4 participates in antigen recognition by binding to nonpolymorphic regions of class II MHC molecules, while the T-cell antigen receptor recognizes a specific peptide antigen that is bound by the MHC molecule (7). The CD4-MHC interaction serves to increase the avidity of the T cell to the antigenpresenting cell but also induces an intracellular signaling event through the CD4-...

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“…47 Cell culture and antibodies The methylcholanthrene-induced fibrosarcoma MethA (BALB/c origin) was maintained in vitro in RPMI-1640 medium supplemented with 10% FBS and antibiotics and occasionally in vivo passage. D10, 48 A.E7, 49 and Clone 19 50 cells have been described previously. An IL-2-dependent murine cytotoxic cell line CTLL-2 and its IL-4-dependent variant CT.4S 51 were obtained from Dr Charles Janeway Jr (Yale University, CT, USA), and maintained in Click's EHAA medium supplemented with 10% FBS and IL-4 (100 U/ml) or IL-2 (10 U/ml), respectively.…”

Section: Micementioning

confidence: 99%

Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity

Kim

Sonn

et al. 2000

Gene Ther

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Local cytokine concentrations are required for inhibition of tumor growth with less toxic side-effects. However, genetically engineered tumor cells secreting cytokines still induce toxicity and activate bystander cells. To circumvent such problems, membrane-bound forms of IL-4 (IL-4m) were expressed on MethA fibrosarcoma tumor cells. Chimeric forms of IL-4 with the type I transmembrane protein CD4 or type II transmembrane protein TNF were designed to express IL-4 in opposite orientations on the tumor cell surface. The IL-4m on tumor clones was able to support cell growth of the IL-4 dependent cytotoxic cell line (CT.4S) and

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Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells.

Cited by 622 publications

References 28 publications

Nuclear repositioning marks the selective exclusion of lineage‐inappropriate transcription factor loci during T helper cell differentiation

Nuclear repositioning marks the selective exclusion of lineage‐inappropriate transcription factor loci during T helper cell differentiation

Elf-1 binds to a critical element in a second CD4 enhancer.

Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity

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