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The contributions of germline-encoded T cell receptor segments and of HLA-DR polymorphisms in shaping the repertoire of human CD4 + CD45RO − T cells were investigated in healthy unrelated Individuals and in patients with rheumatoid arthritis, an HLA-DRB1 ∗ 04associated disease. By comparing frequencies of Vβ-Jβ combinations, healthy Individuals segregated into independent clusters,...
Mice transgenic for SV40 T antigen (Tag) under control of the rat insulin promoter (RIP) develop two alternative immunological phenotypes: tolerance or autoimmunity towards Tag. We utilized the T cell receptor (TCR) genes expressed in a Tag-specific CD4 + cell from an autoimmune RIP-Tag mouse to generate two lines of TCR transgenic mice in which either 10% or 90% of peripheral T cells express...
CD30, a member of the tumor necrosis factor (TNF) receptor family, is expressed constitutively on the surface of the human T cell line ACH-2, which is chronically infected with human Immunodeficiency virus type-1 (HIV)-1. We demonstrate that cross-linking CD30 with an anti-CD30-specific monoclonal antibody, which mimics the described biological activities of the CD30 ligand (CD30L), results in HIV...
The inability of scid pro-B cells to progress to the pre-B and B cell stages is believed to be caused by a defective recombinase activity that fails to resolve chromosomal breaks resulting from attempted V(D)J recombination. In support of this model, we report that certain immunoglobulin transgenes, specifically those which strongly Inhibit endogenous V H -to-DJ H and Vκ-to-Jκ rearrangement...
Herein, we demonstrate that purified Stat1 binds to its tyrosine-phosphorylated docking site on the IFNγ receptor α chain in a direct, specific, and reversible manner. Using surface plasmon resonance, we determine the affinity (K D = 137 nM) and specificity of the interaction and define the minimum affinity needed for receptor-mediated Stat1 activation. In addition, we quantitate the relative...
When B cells are deprived of signaling through CD40, they exhibit the ability to induce T cell tolerance. The in vivo administration of anti-gp39 and allogeneic B cells diminished the ability of mice to mount an allogeneic response. Tolerance induction was specific for the haplotype expressed on the allogeneic B cells. Selective allospecific unresponsiveness was induced in the CD8 and CD4 compartments...
The function of CD3ζ in the assembly and transport of the T cell receptor (TCR)-CD3 complex was analyzed in normal T cells. The ζ chain, but not other chains in the surface TCR complex, rapidly exchanged with newly synthesized ζ. Because ζ was expressed independently from the complex, the TCR complex may be transported to the surface along the ζ turnover pathway by association with ζ. These data suggest...
Using a quantitative multiprobe Southern blot analysis, we demonstrate the surprising result that a significant proportion of αβ T cells and thymocytes retain T cell receptor δ locus sequences. A substantial portion of the retained δ locus is In a fully V-to-D-to-J rearranged configuration and 20% of these δ rearrangements are functional, significantly less than the 33% predicted for random gene rearrangements...
Understanding the immunological mechanisms of protection and pathogenesis in tuberculosis remains problematic. We have examined the extent to which tumor necrosis factor-α (TNFα) contributes to this disease using murine models In which the action of TNFα is inhibited. TNFa was neutralized In vivo by monoclonal antibody; in addition, a mouse strain with a disruption in the gene for the 55 kDa TNF receptor...
Developmental commitment to Th1 or Th2 responses critically Influences host susceptibility to particular pathogens. We describe a novel mechanism governing stable commitment to Th2 differentiation. Naive T cells develop strongly polarized Th1 and Th2 profiles by 7 days after activation. However, commitment of these developing cells differs substantially. Although IL-4 reverses early Th1 differentiation,...
Latent and activated forms of Stat1 and Stat6 have been expressed and purified, enabling biochemical experiments relating to their functional activities. Stat1 bound to a phosphotyrosine peptide derived from the IFNγ receptor with a K D of 50 nM, whereas Stat6 bound to an IL-4 receptor peptide with a K D of 300 nM. Stat-receptor peptide interactions were specific and dependent upon...
Positive selection of functional CD8 + T cells expressing an MHC class I-restricted T cell receptor can be induced in fetal thymus organ culture by class I-binding peptides related to the antigenic peptide ligand. Peptides that act as antagonist or weak agonist/antagonist ligands for mature T cells work efficiently in this regard. In the present study, we have investigated whether low concentrations...
We used gene targeting in embryonic stem cells to introduce an IL-1β null allele in mice. The IL-1β-deficient mice develop normally and are apparently healthy and fertile. The IL-1β null mice responded normally in models of contact and delayed-type hypersensitivity or following bacterial endotoxin LPS-induced inflammation. The IL-1β-deficlent mice showed equivalent resistance to Listeria monocytogenes...
Tgϵ26 mice display an arrest very early in T cell development that has a profound effect on the architecture of thymic stromal cells. We have recently demonstrated that transplantation of wild-type bone marrow cells restores the thymic microenvironment of fetal but not adult Tgϵ26 mice. Here, we report that T cell-reconstituted adult Tgϵ26 mice develop a spontaneous wasting syndrome characterized...
The flk2 receptor tyrosine kinase has been implicated in hematopoietic development. Mice deficient in flk2 were generated. Mutants developed into healthy adults with normal mature hematopoietic populations. However, they possessed specific deficiencies in primitive B lymphoid progenitors. Bone marrow transplantation experiments revealed a further deficiency in T cell and myeloid reconstitution by...
MHC class I genes are potently repressed by HIV Tat, which transactivates the HIV LTR. Tat represses class I transcription by binding to complexes associated with a novel promoter element, consisting of Spi-like DNA binding sites. Transcription by other Sp1-dependent promoters, such as MDR1 and the minimal SV40 promoters, is also repressed by Tat, whereas the human β-actin promoter is neither activated...
CD23 is expressed on a variety of haemopoietic cells and displays pleiotropic activities in vitro. We report that in addition to CD21 and IgE, CD23 interacts specifically with the CD11b and CD11c, the α chains of the β2 integrin adhesion molecule complexes CD11b-CD18 and CD11c-C1318, on monocytes. Full-length recombinant CD23 incorporated into fluorescent liposomes was shown to bind to COS cells transfected...
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