Human CD1d molecules present an unknown ligand, mimicked by the synthetic glycosphingolipid α-gal... more Human CD1d molecules present an unknown ligand, mimicked by the synthetic glycosphingolipid α-galactosylceramide (αGC), to a highly conserved NKT cell subset expressing an invariant TCR Vα24-JαQ paired with Vβ11 chain (Vα24+Vβ11+ invariant NK T cell (NKTinv)). The developmental pathway of Vα24+Vβ11+NKTinv is still unclear, but recent studies in mice were consistent with a TCR instructive, rather than a stochastic, model of differentiation. Using CD1d-αGC-tetramers, we demonstrate that in humans, TCR variable domains other than Vα24 and Vβ11 can mediate specific recognition of CD1d-αGC. In contrast to Vα24+Vβ11+NKTinv cells, Vα24−/CD1d-αGC-specific T cells express either CD8αβ or CD4 molecules, but they are never CD4 CD8 double negative. We show that CD8αβ+Vα24−/CD1d-αGC-specific T cells exhibit CD8-dependent specific cytotoxicity and have lower affinity TCRs than Vα24+/CD1d-αGC-specific T cells. In conclusion, our results demonstrate that, contrary to the currently held view, recogn...
International angiology : a journal of the International Union of Angiology, 2015
Aim of the study was to examine the effects of the geko™ device (a portable electical nerve stimu... more Aim of the study was to examine the effects of the geko™ device (a portable electical nerve stimulator) on microcirculatory flow on the dorsum of the foot, and whether this is influenced by lower limb postures and application of a plaster cast. This was a cross-sectional, healthy cohort, open label, physiological response study. In 10 healthy volunteers, aged 19 to 24 years, laser Doppler fluxmetry measurements were made on the dorsum of the foot in four postures: standing (weight bearing and non-weight bearing) and supine lying (with the lower limb horizontal and then elevated). Measurements of flux were made both at rest and during stimulation with the geko™ device applied over the common peroneal nerve, at 1 Hz for 5 minutes in each posture. Repeat measurement were made after the application of a below knee plaster cast. Measures of flux were compared to basal levels assumed to be in supine with limb horizontal, with no cast and an inactive geko™ device. The geko™ device was effe...
The understanding of the genetic and immunological basis of human periodic fever syndromes, in pa... more The understanding of the genetic and immunological basis of human periodic fever syndromes, in particular cryopyrin-associated periodic syndromes (CAPS), has led to important new insights into the pathogenesis of monogenic and complex interleukin-1beta-associated autoinflammatory diseases. Currently the focus of attention is on the nucleotide-binding oligomerization domain (NOD)-like receptors (NLR), which take part in the regulation of the synthesis and maturation of cytokines in the IL-1 families, NOD-signalosomes and inflammasomes.
Human CD1d molecules present an unknown ligand, mimicked by the synthetic glycosphingolipid α-gal... more Human CD1d molecules present an unknown ligand, mimicked by the synthetic glycosphingolipid α-galactosylceramide (αGC), to a highly conserved NKT cell subset expressing an invariant TCR Vα24-JαQ paired with Vβ11 chain (Vα24+Vβ11+ invariant NK T cell (NKTinv)). The developmental pathway of Vα24+Vβ11+NKTinv is still unclear, but recent studies in mice were consistent with a TCR instructive, rather than a stochastic, model of differentiation. Using CD1d-αGC-tetramers, we demonstrate that in humans, TCR variable domains other than Vα24 and Vβ11 can mediate specific recognition of CD1d-αGC. In contrast to Vα24+Vβ11+NKTinv cells, Vα24−/CD1d-αGC-specific T cells express either CD8αβ or CD4 molecules, but they are never CD4 CD8 double negative. We show that CD8αβ+Vα24−/CD1d-αGC-specific T cells exhibit CD8-dependent specific cytotoxicity and have lower affinity TCRs than Vα24+/CD1d-αGC-specific T cells. In conclusion, our results demonstrate that, contrary to the currently held view, recogn...
International angiology : a journal of the International Union of Angiology, 2015
Aim of the study was to examine the effects of the geko™ device (a portable electical nerve stimu... more Aim of the study was to examine the effects of the geko™ device (a portable electical nerve stimulator) on microcirculatory flow on the dorsum of the foot, and whether this is influenced by lower limb postures and application of a plaster cast. This was a cross-sectional, healthy cohort, open label, physiological response study. In 10 healthy volunteers, aged 19 to 24 years, laser Doppler fluxmetry measurements were made on the dorsum of the foot in four postures: standing (weight bearing and non-weight bearing) and supine lying (with the lower limb horizontal and then elevated). Measurements of flux were made both at rest and during stimulation with the geko™ device applied over the common peroneal nerve, at 1 Hz for 5 minutes in each posture. Repeat measurement were made after the application of a below knee plaster cast. Measures of flux were compared to basal levels assumed to be in supine with limb horizontal, with no cast and an inactive geko™ device. The geko™ device was effe...
The understanding of the genetic and immunological basis of human periodic fever syndromes, in pa... more The understanding of the genetic and immunological basis of human periodic fever syndromes, in particular cryopyrin-associated periodic syndromes (CAPS), has led to important new insights into the pathogenesis of monogenic and complex interleukin-1beta-associated autoinflammatory diseases. Currently the focus of attention is on the nucleotide-binding oligomerization domain (NOD)-like receptors (NLR), which take part in the regulation of the synthesis and maturation of cytokines in the IL-1 families, NOD-signalosomes and inflammasomes.
Uploads
Papers by Stephan Gadola