Spintronic terahertz emitters promise terahertz sources with an unmatched broad frequency bandwidth that are easy to fabricate and operate, and therefore easy to scale at low cost. However, current experiments and proofs of concept rely on free-space ultrafast pump lasers and rather complex benchtop setups. This contrasts with the requirements of widespread industrial applications, where robust, compact, and safe designs are needed.
View Article and Find Full Text PDFUnlabelled: Pasquier, Mathieu, Louis Marxer, Hervé Duplain, Vincent Frochaux, Florence Selz, Pierre Métrailler, Grégoire Zen Ruffinen, and Olivier Hugli. Indications and outcomes of helicopter rescue missions in alpine mountain huts: A retrospective study. High Alt Med Biol 18:355-362, 2017.
View Article and Find Full Text PDFA four-month-old boy with primary immunodeficiency was found to have a homozygous germ-line mutation of the gene encoding the CD3zeta subunit of the T-cell receptor-CD3 complex. CD3zeta is necessary for the development and function of T cells. Some of the patient's T cells had low levels of the T-cell receptor-CD3 complex and carried the Q70X mutation in both alleles of CD3zeta, whereas other T cells had normal levels of the complex and bore the Q70X mutation on only one allele of CD3zeta, plus one of three heterozygous somatic mutations of CD3zeta on the other allele, allowing expression of poorly functional T-cell receptor-CD3 complexes.
View Article and Find Full Text PDFBackground: Impaired Fas-induced apoptosis of lymphocytes in vitro is a principal feature of the autoimmune lymphoproliferative syndrome (ALPS). We studied six children with ALPS whose lymphocytes had normal sensitivity to Fas-induced apoptosis in vitro.
Methods: Susceptibility to Fas-mediated apoptosis and the Fas gene were analyzed in purified subgroups of T cells and other mononuclear cells from six patients with ALPS type III.
Considerable progress has been recently accomplished in the management of patients who have undergone haplo-incompatible haematopoietic stem cell transplantation (HSCT) in terms of intake and prevention of graft-versus-host disease. Nevertheless haplo-incompatible HSCT is a procedure limited to a small number of patients because of the long-lasting immunodeficiency that is responsible for more than 50% of deaths within the first 3 months. Interleukin (IL)-7, which plays a unique and key role in T-cell development both in the mouse and in the human, is particularly attractive for attempting to speed up T-cell reconstitution.
View Article and Find Full Text PDFAffinity maturation of the Ab repertoire in germinal centers leads to the selection of high affinity Abs with selected heavy chain constant regions. Ab maturation involves two modifications of the Ig genes, i.e.
View Article and Find Full Text PDFMHC class II deficiency is a combined immunodeficiency caused by defects in the four regulatory factors, CIITA, RFXANK, RFX5 and RFXAP, that control MHC II expression at the transcriptional level. The RFXANK gene encodes one subunit of the heterotrimeric RFX complex that is involved in the assembly of several transcription factors on MHC II promoters. Seven different RFXANK mutations have previously been reported in 26 unrelated patients.
View Article and Find Full Text PDFThe expression of MHC class II molecules is essential for all Ag-dependent immune functions and is regulated at the transcriptional level. Four trans-acting proteins control the coordinate expression of MHC class II molecules: class II trans-activator (CIITA), regulatory factor binding to the X box (RFX)-associated protein; RFX protein containing ankyrin repeats, and RFX5. In humans, defects in these genes result in MHC class II expression deficiency and cause combined immunodeficiency.
View Article and Find Full Text PDFMurine gut intraepithelial (IEL) T cell receptor (TCR)-alpha/beta lymphocytes bearing CD8alpha/13 or CD8alpha/alpha coreceptors have been shown previously to express different oligoclonal TCR beta chain repertoires in the same mouse, in agreement with other evidence indicating that these two populations belong to different ontogenic lineages, with only CD8alpha/beta+ IELs being fully thymus dependent. CD8alpha/beta+, but not CD8alpha/alpha+, T lymphocytes are also present in the lamina propria. Here, we show that CD8alpha/beta+ lymphocytes from the lamina propria and the epithelium are both oligoclonal, and that they share the same TCR-beta clonotypes in the same mouse, as is also the case for CD4alpha T cells.
View Article and Find Full Text PDFSevere combined immunodeficiency-X1 (SCID-X1) is an X-linked inherited disorder characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the gammac cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which participates in the delivery of growth, survival, and differentiation signals to early lymphoid progenitors. After preclinical studies, a gene therapy trial for SCID-X1 was initiated, based on the use of complementary DNA containing a defective gammac Moloney retrovirus-derived vector and ex vivo infection of CD34+ cells.
View Article and Find Full Text PDFOmenn's syndrome is an inherited human combined immunodeficiency condition characterized by the presence of a large population of activated and tissue-infiltrating T cells. Analysis of the TCRB repertoire revealed a highly restricted TCRBV usage in three patients. More strikingly, T cell clones from the three patients expressed TCRB chains with VDJ junction similarities, suggesting a common antigenic specificity.
View Article and Find Full Text PDFWe have generated two in vivo mouse models to study the regulation of DNA accessibility to the V(D)J recombinase machinery in the T cell receptor (TCR)-J alpha locus. In recombination activating gene (RAG)-deficient mice, both injection of a TCR-beta chain transgene (RTB mice) or anti-CD3-epsilon treatment in vivo (RT3 mice) lead to the same phenotype with homogeneous thymocyte populations blocked at the CD4+ CD8+ double positive (DP) stage. At this developmental stage, the TCR-alpha rearrangements are about to start, and the TCR-J alpha locus is frozen in an accessible but yet unrearranged configuration in these mice.
View Article and Find Full Text PDFNatural killer (NK) cells are characterized by their ability to mediate spontaneous cytotoxicity against susceptible tumor cells and infected cells. They differentiate from hematopoietic progenitor cells. Patients with X-linked severe combined immunodeficiency (SCID X1) carry mutations in the gamma c cytokine receptor gene that result in lack of both T and NK cells.
View Article and Find Full Text PDFTo address the role of the TEA germline transcription, which initiates upstream of the TCR-J alpha S, in the regulation of TCR-J alpha locus accessibility, we created a mouse in which this region has been removed by homologous recombination. Normal development of T alpha beta cells and the expression of other TCR alpha germline transcripts in TEA-/- mice ruled out an exclusive role for TEA in the overall accessibility of the J alpha cluster. However, the rearrangement of the most 5' J alpha (J alpha 61 to J alpha 53) was severely impaired, indicating that TEA may control the DNA accessibility of a particular J alpha window.
View Article and Find Full Text PDFGut thymo-dependent (CD8 alpha + beta + or CD4+) or -independent (CD8 alpha + beta -) intraepithelial lymphocytes (IEL) mediate cytotoxicity following T cell receptor (TCR)-CD3 signaling, but only TCR gamma delta + and alpha beta + thymo-independent IEL show cytotoxicity of natural killer (NK) and antibody-dependent cell-mediated cytotoxicity types. Moreover, TCR alpha beta + and gamma delta + thymo-independent IEL express NK receptors, and may therefore be referred to as NK-TIEL. NK-TIEL cytotoxicity is mediated through perforin, Fas, or both pathways.
View Article and Find Full Text PDFWe have previously shown by means of fluorescence microscopy that antigen-independent adhesion of resting CD4 T cells to EBV-transformed B cells can be down-regulated by ligand interaction with CD4. In this study we used flow cytometry analysis of conjugate formation to confirm these findings. No conjugates between resting CD4 + T cells and B cells were initially detected in the latter method, because flow velocity in the flow chamber induces hydrodynamic elongation forces which disrupt low-affinity conjugates.
View Article and Find Full Text PDFDendritic cells (DC) are the main antigen-presenting cells for the initiation of primary T cell-mediated immune responses. In the first stage of activation, T cells bind to DC in an antigen-independent manner. We studied the adhesion characteristics of human CD4+ T cells to DC generated from CD34+ hematopoietic progenitors following 12 to 13 days of culture in the presence of granulocyte/macrophage colony-stimulating factor and tumor necrosis factor-alpha.
View Article and Find Full Text PDFMost gut intraepithelial cells (IEL) of the mouse are T cells that bear CD8 molecules, present either as alpha-beta chain heterodimers (CD8 beta+) or as alpha chain homodimers (CD8 beta-). All CD8 beta+ IEL bear alpha/beta T cell receptors (TCR); CD8 beta- IEL bear either alpha/beta or gamma/delta TCR and are considered to be a thymus-independent (TI) population, probably arising locally from a small fraction of CD3- IEL containing the recombinant activating gene RAG proteins. Here we report that TI CD8 beta- IEL, whether bearing alpha/beta or gamma/delta TCR, contain, in normal mice, mRNAs for both zeta and Fc epsilon RI gamma chains.
View Article and Find Full Text PDFRev Med Suisse Romande
February 1994
The human T cell receptor was studied using an anchored-polymerase chain reaction (A-PCR) and hybridization with V beta-specific oligonucleotide probes, together with the few anti-V beta monoclonal antibodies (mAb) available. After confirming the semiquantitative and reproducible nature of the A-PCR technique, we assessed the complete V beta repertoire in sorted CD4+ and CD8+ lymphocyte populations from three normal donors. These experiments confirmed the absence of V beta-restricted deletions in human peripheral cells, in contrast to several mouse strains.
View Article and Find Full Text PDFThe effects of iron deficiency on immunity remain controversial. This study was designed to assess the impact of iron supplementation on the immune status, in 81 children aged 6 months-3 years, at high risk for iron deficiency, using a longitudinal double blind randomised and placebo-controlled study. Lymphocytes of iron-deficient children produced less interleukin-2 in vitro.
View Article and Find Full Text PDFThe presence of transcripts of the recombination activating gene RAG-1 was studied by in situ hybridization on selected populations of murine thymocytes, peripheral lymphocytes and gut intraepithelial lymphocytes (IEL), obtained by cell sorting. RAG-1 mRNA was found in a majority of "double-positive" (DP) thymocytes, but was absent in "single-positive" thymocytes and peripheral T lymphocytes. The only other T lineages in which about 10%-20% of the cells contained RAG-1 mRNA, and in smaller amounts, were "double-negative" (DN), T cell receptor (TcR) gamma delta- cortical thymocytes and gut CD3- IEL.
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