108 research outputs found
Hydrophobic CDR3 residues promote the development of self-reactive T cells
Studies of individual T cell antigen receptors (TCRs) have shed some light on structural features that underlie self-reactivity. However, the general rules that can be used to predict whether TCRs are self-reactive have not been fully elucidated. Here we found that the interfacial hydrophobicity of amino acids at positions 6 and 7 of the complementarity-determining region CDR3β robustly promoted the development of self-reactive TCRs. This property was found irrespective of the member of the β-chain variable region (V[subscript β]) family present in the TCR or the length of the CDR3β. An index based on these findings distinguished V[subscript β]2[superscript +], V[subscript β]6[superscript +] and V[subscript β]8.2[superscript +] regulatory T cells from conventional T cells and also distinguished CD4[superscript +] T cells selected by the major histocompatibility complex (MHC) class II molecule I-A[superscript g7] (associated with the development of type 1 diabetes in NOD mice) from those selected by a non–autoimmunity-promoting MHC class II molecule I-Ab. Our results provide a means for distinguishing normal T cell repertoires versus autoimmunity-prone T cell repertoires
CHARACTERISTICS OF THE INCREASED ADRENOCORTICAL FUNCTION OBSERVED IN MANY OBESE PATIENTS *
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75360/1/j.1749-6632.1965.tb34805.x.pd
Contribution by Polymorphonucleate Granulocytes to Elevated Gamma-Glutamyltransferase in Cystic Fibrosis Sputum
Background: Cystic fibrosis (CF) is an autosomal recessive disorder characterized by a chronic neutrophilic airways
inflammation, increasing levels of oxidative stress and reduced levels of antioxidants such as glutathione (GSH). Gammaglutamyltransferase
(GGT), an enzyme induced by oxidative stress and involved in the catabolism of GSH and its derivatives,
is increased in the airways of CF patients with inflammation, but the possible implications of its increase have not yet been
investigated in detail.
Principal Findings: The present study was aimed to evaluate the origin and the biochemical characteristics of the GGT
detectable in CF sputum. We found GGT activity both in neutrophils and in the fluid, the latter significantly correlating with
myeloperoxidase expression. In neutrophils, GGT was associated with intracellular granules. In the fluid, gel-filtration
chromatography showed the presence of two distinct GGT fractions, the first corresponding to the human plasma b-GGT
fraction, the other to the free enzyme. The same fractions were also observed in the supernatant of ionomycin and fMLPactivated
neutrophils. Western blot analysis confirmed the presence of a single band of GGT immunoreactive peptide in the
CF sputum samples and in isolated neutrophils.
Conclusions: In conclusion, our data indicate that neutrophils are able to transport and release GGT, thus increasing GGT
activity in CF sputum. The prompt release of GGT may have consequences on all GGT substrates, including major
inflammatory mediators such as S-nitrosoglutathione and leukotrienes, and could participate in early modulation of
inflammatory response
Attenuated T Cell Responses to a High-Potency Ligand In Vivo
According to this study, the strongest T cell receptor ligands in vitro do not necessarily induce the strongest T cell responses in vivo, suggesting that vaccine designers may need to reconsider their strategies
Oligodendrocytes: biology and pathology
Oligodendrocytes are the myelinating cells of the central nervous system (CNS). They are the end product of a cell lineage which has to undergo a complex and precisely timed program of proliferation, migration, differentiation, and myelination to finally produce the insulating sheath of axons. Due to this complex differentiation program, and due to their unique metabolism/physiology, oligodendrocytes count among the most vulnerable cells of the CNS. In this review, we first describe the different steps eventually culminating in the formation of mature oligodendrocytes and myelin sheaths, as they were revealed by studies in rodents. We will then show differences and similarities of human oligodendrocyte development. Finally, we will lay out the different pathways leading to oligodendrocyte and myelin loss in human CNS diseases, and we will reveal the different principles leading to the restoration of myelin sheaths or to a failure to do so
Interactive effects of a common γ-glutamyltransferase 1 variant and low high-density lipoprotein-cholesterol on diabetic macro- and micro-angiopathy
Heterogeneity of induced testicular interstitial cell tumors of mice as evidenced by steroid biosynthetic enzyme activities.
In vivo and in vitro studies of steroid production by a luteoma and an adrenal cortical carcinoma in mice.
Dna synthesis and dna polymerase activity in leydig cells of diethylstilbestrol-stimulated mouse testes.
- …