Lymphoid Development in Mice Congenitally Lacking T Cell Receptor αβ-Expressing Cells

Philpott, Karen L.; Viney, Joanne L.; Kay, Graham F.; Rastan, Sohaila; Gardiner, Edith M.; Chae, Sarah; Hayday, Adrian; Owen, Michael John

doi:10.1126/science.1604321

Cited by 340 publications

(191 citation statements)

References 38 publications

Supporting

Mentioning

179

Contrasting

Order By: Relevance

“…APC were splenic cells ( G 85% B cells) from TCR § -/-mice [36] obtained following erythrocyte lysis of splenocytes and were loaded with peptide in RPMI plus 10% FCS for 1 h at 37°C, washed twice, and incubated in RPMI plus 10% FCS at 2×10 6 cells/ml for 15 h in the presence of an equal concen-tration of thymocytes. Levels of CD4 and CD8 on the thymocytes were determined by flow cytometry.…”

Section: Cd4 and Cd8 Down-modulationmentioning

confidence: 99%

Vav1 transduces TCR signals required for LFA‐1 function and cell polarization at the immunological synapse

et al. 2003

View full text Add to dashboard Cite

Activation of T lineage cells through the TCR by peptide-MHC complexes on APC is critically dependent on rearrangement of the actin cytoskeleton. Vav1 is a guanine nucleotide exchange factor for members of the Rho/Rac family of GTPases which is activated following TCR stimulation, suggesting that it may transduce TCR signals to the activation of some or all actin-controlled processes. We show that Vav1-deficient double-positive thymocytes are less efficient at forming conjugates with APC presenting agonist peptide than wild-type cells are. Furthermore we demonstrate that Vav1 is required for TCR-induced activation of the integrin LFA-1, which is likely to explain the defect in conjugate formation. However, once Vav1-deficient cells form a conjugate, the assembly of proteins into an immunological synapse at the conjugate interface is normal. In contrast, thymocyte polarization is defective in the absence of Vav1, as judged by the relocalization of the microtubule-organizing center. These data demonstrate that Vav1 transduces signals to only a subset of cytoskeletondependent events at the immunological synapse.

show abstract

Section: Cd4 and Cd8 Down-modulationmentioning

confidence: 99%

Vav1 transduces TCR signals required for LFA‐1 function and cell polarization at the immunological synapse

et al. 2003

View full text Add to dashboard Cite

show abstract

“…C57BL/6 mice were obtained from Charles River Breeding Laboratories (Calco, Italy) and Harlan Breeders (Zeist, The Netherlands). TCR C␣ Ϫ/Ϫ mice (27), backcrossed seven generations onto C57BL/6 mice, were obtained from Centre de Distribution, Typage and Archivage animal-Centre National de la Recherche Scientifique (Orleans, France). J␣18 Ϫ/Ϫ mice (kindly provided by Prof. M. Taniguchi, Chiba University School of Medicine, Chiba, Japan) were backcrossed eight times onto C57BL/6 mice (16).…”

Section: Transgenic and Mutant Micementioning

confidence: 99%

Human Invariant Vα24-JαQ TCR Supports the Development of CD1d-Dependent NK1.1+ and NK1.1− T Cells in Transgenic Mice

Capone

Cantarella

Schumann

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

A sizable fraction of T cells expressing the NK cell marker NK1.1 (NKT cells) bear a very conserved TCR, characterized by homologous invariant (inv.) TCR Vα24-JαQ and Vα14-Jα18 rearrangements in humans and mice, respectively, and are thus defined as inv. NKT cells. Because human inv. NKT cells recognize mouse CD1d in vitro, we wondered whether a human inv. Vα24 TCR could be selected in vivo by mouse ligands presented by CD1d, thereby supporting the development of inv. NKT cells in mice. Therefore, we generated transgenic (Tg) mice expressing the human inv. Vα24-JαQ TCR chain in all T cells. The expression of the human inv. Vα24 TCR in TCR Cα−/− mice indeed rescues the development of inv. NKT cells, which home preferentially to the liver and respond to the CD1d-restricted ligand α-galactosylceramide (α-GalCer). However, unlike inv. NKT cells from non-Tg mice, the majority of NKT cells in Vα24 Tg mice display a double-negative phenotype, as well as a significant increase in TCR Vβ7 and a corresponding decrease in TCR Vβ8.2 use. Despite the forced expression of the human CD1d-restricted TCR in Cα−/− mice, staining with mCD1d-α-GalCer tetramers reveals that the absolute numbers of peripheral CD1d-dependent T lymphocytes increase at most by 2-fold. This increase is accounted for mainly by an increased fraction of NK1.1− T cells that bind CD1d-α-GalCer tetramers. These findings indicate that human inv. Vα24 TCR supports the development of CD1d-dependent lymphocytes in mice, and argue for a tight homeostatic control on the total number of inv. NKT cells. Thus, human inv. Vα24 TCR-expressing mice are a valuable model to study different aspects of the inv. NKT cell subset.

show abstract

“…BALB/c, Stat4-deficient (17) BALB/c, and Stat6-deficient (18) BALB/c mice (The Jackson Laboratory, Bar Harbor, ME), IL-4R␣-deficient BALB/c (19), tenth backcross TCR-C␣-deficient mice (20), IL-4 greenenhanced transcript (4get) 4 IL-4 reporter mice (21), and CTLA-4-deficient mice (22) were kept in the University of California, San Francisco specific pathogen-free barrier facility in accordance with institutional guidelines.…”

Section: Micementioning

confidence: 99%

Stat Signals Release Activated Naive Th Cells from an Anergic Checkpoint

Mohrs

Lacy

Locksley

2003

The Journal of Immunology

View full text Add to dashboard Cite

Activation of naive Th lymphocytes by the TCR and the costimulatory molecule, CD28, is believed to provide competent signals for differentiation to effector cells. Such activated cells proliferated and expressed IL-2, but arrested in an immature state maintained by CTLA-4. Although unresponsive to restimulation by TCR/CD28 alone, restimulation with TCR/CD28 and either Stat4- or Stat6-mediated cytokine signals rescued cells to proliferate and differentiate to the appropriately matched canonical Th subsets. Addition of IL-4 at defined periods revealed that naive T cells were receptive to IL-4-mediated differentiation for up to 3 days after their initial priming. A Stat-dependent anergic checkpoint between clonal expansion and effector cell differentiation may defer the cytokine profile to be instructed at the site of infection, thus preventing the unregulated development of potentially damaging effector cells.

show abstract

Lymphoid Development in Mice Congenitally Lacking T Cell Receptor αβ-Expressing Cells

Cited by 340 publications

References 38 publications

Vav1 transduces TCR signals required for LFA‐1 function and cell polarization at the immunological synapse

Vav1 transduces TCR signals required for LFA‐1 function and cell polarization at the immunological synapse

Human Invariant Vα24-JαQ TCR Supports the Development of CD1d-Dependent NK1.1+ and NK1.1− T Cells in Transgenic Mice

Stat Signals Release Activated Naive Th Cells from an Anergic Checkpoint

Contact Info

Product

Resources

About