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Results: 1 to 10 of 27

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How Superantigens Bind MHC.
Van Kaer L
(2018) J Immunol 201: 1817-1818
MeSH Terms: Animals, Antigens, Bacterial, Clonal Deletion, Enterotoxins, Histocompatibility Antigens, Humans, Lymphocyte Activation, Minor Lymphocyte Stimulatory Antigens, Peptide Fragments, Protein Binding, Receptors, Antigen, T-Cell, alpha-beta, Superantigens, T-Lymphocytes
Added March 26, 2019
0 Communities
1 Members
0 Resources
13 MeSH Terms
Histone Deacetylase 3 Is Required for Efficient T Cell Development.
Stengel KR, Zhao Y, Klus NJ, Kaiser JF, Gordy LE, Joyce S, Hiebert SW, Summers AR
(2015) Mol Cell Biol 35: 3854-65
MeSH Terms: Animals, CD4 Antigens, CD4-Positive T-Lymphocytes, CD8 Antigens, CD8-Positive T-Lymphocytes, Cell Differentiation, Gene Deletion, Gene Expression Regulation, Developmental, Histone Deacetylases, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Proto-Oncogene Proteins c-bcl-2, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, bcl-X Protein
Show Abstract · Added September 28, 2015
Hdac3 is a key target for Hdac inhibitors that are efficacious in cutaneous T cell lymphoma. Moreover, the regulation of chromatin structure is critical as thymocytes transition from an immature cell with open chromatin to a mature T cell with tightly condensed chromatin. To define the phenotypes controlled by Hdac3 during T cell development, we conditionally deleted Hdac3 using the Lck-Cre transgene. This strategy inactivated Hdac3 in the double-negative stages of thymocyte development and caused a significant impairment at the CD8 immature single-positive (ISP) stage and the CD4/CD8 double-positive stage, with few mature CD4(+) or CD8(+) single-positive cells being produced. When Hdac3(-/-) mice were crossed with Bcl-xL-, Bcl2-, or TCRβ-expressing transgenic mice, a modest level of complementation was found. However, when the null mice were crossed with mice expressing a fully rearranged T cell receptor αβ transgene, normal levels of CD4 single-positive cells were produced. Thus, Hdac3 is required for the efficient transit from double-negative stage 4 through positive selection.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
1 Communities
2 Members
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18 MeSH Terms
The transcriptional repressor NKAP is required for the development of iNKT cells.
Thapa P, Das J, McWilliams D, Shapiro M, Sundsbak R, Nelson-Holte M, Tangen S, Anderson J, Desiderio S, Hiebert S, Sant'angelo DB, Shapiro VS
(2013) Nat Commun 4: 1582
MeSH Terms: Animals, Cell Survival, Gene Deletion, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, Histone Deacetylases, Mice, Mice, Knockout, Natural Killer T-Cells, Organ Specificity, Receptors, Antigen, T-Cell, alpha-beta, Receptors, Notch, Recombination, Genetic, Repressor Proteins, Thymocytes
Show Abstract · Added March 26, 2014
Invariant natural killer T cells have a distinct developmental pathway from conventional αβ T cells. Here we demonstrate that the transcriptional repressor NKAP is required for invariant natural killer T cell but not conventional T cell development. In CD4-cre NKAP conditional knockout mice, invariant natural killer T cell development is blocked at the double-positive stage. This cell-intrinsic block is not due to decreased survival or failure to rearrange the invariant Vα14-Jα18 T cell receptor-α chain, but is rescued by overexpression of a rec-Vα14-Jα18 transgene at the double-positive stage, thus defining a role for NKAP in selection into the invariant natural killer T cell lineage. Importantly, deletion of the NKAP-associated protein histone deacetylase 3 causes a similar block in the invariant natural killer T cell development, indicating that NKAP and histone deacetylase 3 functionally interact to control invariant natural killer T cell development.
1 Communities
1 Members
0 Resources
14 MeSH Terms
A mouse model of clonal CD8+ T lymphocyte-mediated alopecia areata progressing to alopecia universalis.
Alli R, Nguyen P, Boyd K, Sundberg JP, Geiger TL
(2012) J Immunol 188: 477-86
MeSH Terms: Alopecia Areata, Animals, CD8-Positive T-Lymphocytes, Hair Follicle, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, Humans, Interleukin-10, Interleukin-17, Interleukin-4, Lymphocyte Activation, Mice, Mice, Knockout, Rats, Receptors, Antigen, T-Cell, alpha-beta
Show Abstract · Added March 20, 2014
Alopecia areata is among the most prevalent autoimmune diseases, yet compared with other autoimmune conditions, it is not well studied. This in part results from limitations in the C3H/HeJ mouse and DEBR rat model systems most commonly used to study the disease, which display a low frequency and late onset. We describe a novel high-incidence model for spontaneous alopecia areata. The 1MOG244 T cell expresses dual TCRA chains, one of which, when combined with the single TCRB present, promotes the development of CD8(+) T cells with specificity for hair follicles. Retroviral transgenic mice expressing this TCR develop spontaneous alopecia areata at nearly 100% incidence. Disease initially follows a reticular pattern, with regionally cyclic episodes of hair loss and regrowth, and ultimately progresses to alopecia universalis. Alopecia development is associated with CD8(+) T cell activation, migration into the intrafollicular region, and hair follicle destruction. The disease may be adoptively transferred with T lymphocytes and is class I and not class II MHC-dependent. Pathologic T cells primarily express IFNG and IL-17 early in disease, with dramatic increases in cytokine production and recruitment of IL-4 and IL-10 production with disease progression. Inhibition of individual cytokines did not significantly alter disease incidence, potentially indicating redundancy in cytokine responses. These results therefore characterize a new high-incidence model for alopecia areata in C57BL/6J mice, the first to our knowledge to apply a monoclonal TCR, and indicate that class I MHC-restricted CD8(+) T lymphocytes can independently mediate the pathologic response.
1 Communities
1 Members
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15 MeSH Terms
Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension.
Marvar PJ, Thabet SR, Guzik TJ, Lob HE, McCann LA, Weyand C, Gordon FJ, Harrison DG
(2010) Circ Res 107: 263-70
MeSH Terms: Administration, Oral, Adoptive Transfer, Angiotensin II, Animals, Antihypertensive Agents, Blood Pressure, Disease Models, Animal, Genes, T-Cell Receptor alpha, Genes, T-Cell Receptor beta, Homeodomain Proteins, Hydralazine, Hypertension, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Norepinephrine, Receptors, Antigen, T-Cell, alpha-beta, Superoxides, T-Lymphocytes, Third Ventricle, Time Factors, Vasculitis
Show Abstract · Added December 10, 2013
RATIONALE - We have previously found that T lymphocytes are essential for development of angiotensin II-induced hypertension; however, the mechanisms responsible for T-cell activation in hypertension remain undefined.
OBJECTIVE - We sought to study the roles of the CNS and pressure elevation in T-cell activation and vascular inflammation caused by angiotensin II.
METHODS AND RESULTS - To prevent the central actions of angiotensin II, we created anteroventral third cerebral ventricle (AV3V) lesions in mice. The elevation in blood pressure in response to angiotensin II was virtually eliminated by AV3V lesions, as was activation of circulating T cells and the vascular infiltration of leukocytes. In contrast, AV3V lesioning did not prevent the hypertension and T-cell activation caused by the peripheral acting agonist norepinephrine. To determine whether T-cell activation and vascular inflammation are attributable to central influences or are mediated by blood pressure elevation, we administered hydralazine (250 mg/L) in the drinking water. Hydralazine prevented the hypertension and abrogated the increase in circulating activated T cells and vascular infiltration of leukocytes caused by angiotensin II.
CONCLUSIONS - We conclude that the central and pressor effects of angiotensin II are critical for T-cell activation and development of vascular inflammation. These findings also support a feed-forward mechanism in which modest degrees of blood pressure elevation lead to T-cell activation, which in turn promotes inflammation and further raises blood pressure, leading to severe hypertension.
1 Communities
1 Members
0 Resources
24 MeSH Terms
Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands.
Florence WC, Xia C, Gordy LE, Chen W, Zhang Y, Scott-Browne J, Kinjo Y, Yu KO, Keshipeddy S, Pellicci DG, Patel O, Kjer-Nielsen L, McCluskey J, Godfrey DI, Rossjohn J, Richardson SK, Porcelli SA, Howell AR, Hayakawa K, Gapin L, Zajonc DM, Wang PG, Joyce S
(2009) EMBO J 28: 3579-90
MeSH Terms: Adaptation, Biological, Animals, Antigen Presentation, Antigens, CD1d, Antigens, Tumor-Associated, Carbohydrate, Cells, Cultured, Galactosylceramides, Ligands, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Models, Molecular, Natural Killer T-Cells, Receptors, Antigen, T-Cell, Receptors, Antigen, T-Cell, alpha-beta, Structure-Activity Relationship, T-Cell Antigen Receptor Specificity
Show Abstract · Added May 19, 2014
The semi-invariant natural killer (NK) T-cell receptor (NKTcr) recognises structurally diverse glycolipid antigens presented by the monomorphic CD1d molecule. While the alpha-chain of the NKTcr is invariant, the beta-chain is more diverse, but how this diversity enables the NKTcr to recognise diverse antigens, such as an alpha-linked monosaccharide (alpha-galactosylceramide and alpha-galactosyldiacylglycerol) and the beta-linked trisaccharide (isoglobotriaosylceramide), is unclear. We demonstrate here that NKTcrs, which varied in their beta-chain usage, recognised diverse glycolipid antigens with a similar binding mode on CD1d. Nevertheless, the NKTcrs recognised distinct epitopic sites within these antigens, including alpha-galactosylceramide, the structurally similar alpha-galactosyldiacylglycerol and the very distinct isoglobotriaosylceramide. We also show that the relative roles of the CDR loops within the NKTcr beta-chain varied as a function of the antigen. Thus, while NKTcrs characteristically use a conserved docking mode, the NKTcr beta-chain allows these cells to recognise unique aspects of structurally diverse CD1d-restricted ligands.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease.
Olivares-Villagómez D, Mendez-Fernandez YV, Parekh VV, Lalani S, Vincent TL, Cheroutre H, Van Kaer L
(2008) Proc Natl Acad Sci U S A 105: 17931-6
MeSH Terms: Animals, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Proliferation, Colitis, Colon, Disease Models, Animal, Epithelium, Homeostasis, Immunologic Memory, Inflammatory Bowel Diseases, Lymphocyte Count, Lymphocytes, Lymphocytic choriomeningitis virus, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, alpha-beta
Show Abstract · Added December 10, 2013
Intestinal intraepithelial lymphocytes (IEL) bear a partially activated phenotype that permits them to rapidly respond to antigenic insults. However, this phenotype also implies that IEL must be highly controlled to prevent misdirected immune reactions. It has been suggested that IEL are regulated through the interaction of the CD8alpha alpha homodimer with the thymus leukemia (TL) antigen expressed by intestinal epithelial cells. We have generated and characterized mice genetically-deficient in TL expression. Our findings show that TL expression has a critical role in maintaining IEL effector functions. Also, TL deficiency accelerated colitis in a genetic model of inflammatory bowel disease. These findings reveal an important regulatory role of TL in controlling IEL function and intestinal inflammation.
1 Communities
2 Members
0 Resources
18 MeSH Terms
Mice depleted of alphabeta but not gammadelta T cells are resistant to mortality caused by cecal ligation and puncture.
Enoh VT, Lin SH, Lin CY, Toliver-Kinsky T, Murphey ED, Varma TK, Sherwood ER
(2007) Shock 27: 507-19
MeSH Terms: Animals, Anti-Bacterial Agents, Bacteremia, Bacteria, Cecum, Chemokine CXCL2, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Imipenem, Interleukin-6, Killer Cells, Natural, Ligation, Mice, Mice, Inbred C57BL, Mice, Knockout, Monokines, Punctures, Receptors, Antigen, T-Cell, alpha-beta, Receptors, Antigen, T-Cell, gamma-delta, Sepsis, T-Lymphocytes, Temperature, Time Factors
Show Abstract · Added October 18, 2015
The present study was undertaken to determine whether the mice depleted of alphabeta or gammadelta T cells show resistance to acute polymicrobial sepsis caused by cecal ligation and puncture (CLP). T-cell receptor beta knockout (betaTCRKO) and T-cell receptor delta knockout (deltaTCRKO) mice were used. An additional group of mice was treated with an antibody against the alphabeta T-cell receptor to induce alphabeta T-cell depletion; a subset of alphabeta T cell-deficient mice was also treated with anti-asialoGM1 to deplete natural killer (NK) cells. The mice underwent CLP and were monitored for survival, temperature, acid-base balance, bacterial counts, and cytokine production. The betaTCRKO mice and the wild-type mice treated with anti-beta T-cell receptor (anti-TCRbeta) antibody showed improved survival after CLP compared with wild-type mice. The treatment of alphabeta T cell-deficient mice with anti-asialoGM1further improved survival after CLP, especially when the mice were treated with imipenem. The improved survival observed in alphabeta T cell-deficient mice was associated with less hypothermia, improved acid-base balance, and decreased production of the proinflammatory cytokines interleukin (IL) 6 and macrophage inflammatory protein (MIP) 2. Compared with wild-type controls, the overall survival was not improved in deltaTCRKO mice. The concentrations of IL-6 and MIP-2 in plasma and cytokine mRNA expression in tissues were not significantly different between wild-type and deltaTCRKO mice. These studies indicate that mice depleted of alphabeta but not of gammadelta T cells are resistant to mortality in an acutely lethal model of CLP. The depletion of NK cells caused further survival benefit in alphabeta T cell-deficient mice. These findings suggest that alphabeta T and NK cells mediate or facilitate CLP-induced inflammatory injury.
0 Communities
1 Members
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24 MeSH Terms
Cutting edge: the ontogeny and function of Va14Ja18 natural T lymphocytes require signal processing by protein kinase C theta and NF-kappa B.
Stanic AK, Bezbradica JS, Park JJ, Van Kaer L, Boothby MR, Joyce S
(2004) J Immunol 172: 4667-71
MeSH Terms: Animals, Antigen Presentation, Antigens, CD1, Antigens, CD1d, Cell Differentiation, Cytokines, Galactosylceramides, Hybridomas, Isoenzymes, Killer Cells, Natural, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B, Protein Kinase C, Protein Kinase C-theta, Receptors, Antigen, T-Cell, alpha-beta, Signal Transduction
Show Abstract · Added December 10, 2013
The rapid and robust immunoregulatory cytokine response of Va14Ja18 natural T (iNKT) cells to glycolipid Ags determines their diverse functions. Unlike conventional T cells, iNKT lymphocyte ontogeny absolutely requires NF-kappa B signaling. However, the precise role of NF-kappa B in iNKT cell function and the identity of upstream signals that activate NF-kappa B in this T cell subset remain unknown. Using mice in which iNKT cell ontogeny has been rescued despite inhibition of NF-kappa B signaling, we demonstrate that iNKT cell function requires NF-kappa B in a lymphocyte-intrinsic manner. Furthermore, the ontogeny of functional iNKT cells requires signaling through protein kinase C theta, which is dispensable for conventional T lymphocyte development. The unique requirement of protein kinase C theta implies that signals emanating from the TCR activate NF-kappa B during iNKT cell development and function. Thus, we conclude that NF-kappa B signaling plays a crucial role at distinct levels of iNKT cell biology.
0 Communities
3 Members
0 Resources
19 MeSH Terms
Another view of T cell antigen recognition: cooperative engagement of glycolipid antigens by Va14Ja18 natural T(iNKT) cell receptor [corrected].
Stanic AK, Shashidharamurthy R, Bezbradica JS, Matsuki N, Yoshimura Y, Miyake S, Choi EY, Schell TD, Van Kaer L, Tevethia SS, Roopenian DC, Yamamura T, Joyce S
(2003) J Immunol 171: 4539-51
MeSH Terms: Animals, Antigens, Antigens, CD1, Antigens, CD1d, Cell Line, Clone Cells, Cytotoxicity Tests, Immunologic, Galactosylceramides, Killer Cells, Natural, Kinetics, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, T-Cell, alpha-beta, Sensitivity and Specificity, Sphingosine, Structure-Activity Relationship, T-Lymphocyte Subsets
Show Abstract · Added December 10, 2013
Va14Ja18 natural T (iNKT) cells rapidly elicit a robust effector response to different glycolipid Ags, with distinct functional outcomes. Biochemical parameters controlling iNKT cell function are partly defined. However, the impact of iNKT cell receptor beta-chain repertoire and how alpha-galactosylceramide (alpha-GalCer) analogues induce distinct functional responses have remained elusive. Using altered glycolipid ligands, we discovered that the Vb repertoire of iNKT cells impacts recognition and Ag avidity, and that stimulation with suboptimal avidity Ag results in preferential expansion of high-affinity iNKT cells. iNKT cell proliferation and cytokine secretion, which correlate with iNKT cell receptor down-regulation, are induced within narrow biochemical thresholds. Multimers of CD1d1-alphaGalCer- and alphaGalCer analogue-loaded complexes demonstrate cooperative engagement of the Va14Ja18 iNKT cell receptor whose structure and/or organization appear distinct from conventional alphabeta TCR. Our findings demonstrate that iNKT cell functions are controlled by affinity thresholds for glycolipid Ags and reveal a novel property of their Ag receptor apparatus that may have an important role in iNKT cell activation.
0 Communities
2 Members
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19 MeSH Terms