Lymphokine dependence of in vivo expression of MHC class II antigens by endothelium

Changes in the expression of class II antigens of the major histocompatibility complex (MHC) have an integral role in the regulation of immune responses, and are brought about in vitro by soluble mediators. However, the mechanism that underlies in vivo expression of MHC class II antigens in, for example, endothelial cells in the absence of immunological stimulation has not been studied. We demonstrate here that expression of MHC class II antigens is not a constitutive property of endothelial cells, for MHC class II antigen-positive endothelial cells do not express these antigens during treatment with the immunosuppressive agent cyclosporin A. In vivo MHC class II antigen expression by canine endothelial cells is therefore dependent on factors, probably the lymphokine gamma-interferon produced by the immune system, whose secretion is inhibited by cyclosporin A.     

Pituitary growth hormone and hypothalamic somatostatin in young female rats versus old constant estrous female rats

Pituitary content and concentration of growth hormone was significantly reduced, and hypothalamic somatostatin content significantly increased, in old constant estrous as compared to young female rats. Increased levels of somatostatin may contribute to the decrease in pituitary growth hormone levels in these animals.     

Wound-induced alterations in survival of 60Co irradiated mice: importance of wound timing

Wounding mice shortly before or shortly after lethal 60Co irradiation enhances survival. Survival of wounded-irradiated mice may be due to enhanced hematopoietic recovery as measured by endogenous spleen colony (E-CFU-s) formation.     

Mutations in a delta 8-delta 7 sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata. jderry@immunex.com.

Tattered (Td) is an X-linked, semi-dominant mouse mutation associated with prenatal male lethality. Heterozygous females are small and at 4-5 days of age develop patches of hyperkeratotic skin where no hair grows, resulting in a striping of the coat in adults. Craniofacial anomalies and twisted toes have also been observed in some affected females. A potential second allele of Td has also been described. The phenotype of Td is similar to that seen in heterozygous females with human X-linked dominant chondrodysplasia punctata (CDPX2, alternatively known as X-linked dominant Conradi-Hünermann-Happle syndrome) as well as another X-linked, semi-dominant mouse mutation, bare patches (Bpa). The Bpa gene has recently been identified and encodes a protein with homology to 3beta-hydroxysteroid dehydrogenases that functions in one of the later steps of cholesterol biosynthesis. CDPX2 patients display skin defects including linear or whorled atrophic and pigmentary lesions, striated hyperkeratosis, coarse lusterless hair and alopecia, cataracts and skeletal abnormalities including short stature, rhizomelic shortening of the limbs, epiphyseal stippling and craniofacial defects (MIM 302960). We have now identified the defect in Td mice as a single amino acid substitution in the delta8-delta7 sterol isomerase emopamil binding protein (Ebp; encoded by Ebp in mouse) and identified alterations in human EBP in seven unrelated CDPX2 patients.     

Ultrastructural localization of choline acetyltransferase in vascular endothelial cells in rat brain

Furchgott and Zawadski have shown that acetylcholine (ACh) does not act directly on the smooth muscle of blood vessel walls, but rather via receptors on the endothelial cells lining the lumen, to release an endothelium-derived relaxing factor (EDRF). As it is very unlikely that neurotransmitter released from the periarterial nerves, which are confined to the adventitial-medial border, diffuses all the way through the medial muscle coat before acting on endothelial cells to release EDRF to produce vasodilatation, this discovery has been regarded as an indication of a pathophysiological mechanism, rather than a physiological one (see refs 2, 3). ACh is rapidly degraded in the blood by acetylcholinesterase, so that ACh must be released locally to be effective on endothelial cells. Here we demonstrate the immunocytochemical localization of choline acetyltransferase in endothelial cells of small brain vessels, which is consistent with the view that the ACh originates from endothelial cells that can synthesize and store it. We suggest that release of ACh following damage to endothelial cells during ischaemia contributes to a pathophysiological mechanism of vasodilation which protects that segment of vessel from further damage as well as brain cells from hypoxia.     

Homing receptor-bearing thymocytes, an immunocompetent cortical subpopulation

Much of the differentiation of murine T cells takes place in the thymus, perhaps influenced by the operation of stringent selection mechanisms whose existence has been inferred from the high rate of thymocyte turnover in the absence of extensive emigration. The origin of those 1% of total thymocytes which leave the thymus and seed the peripheral lymphoid organs is obscure. Recent thymic emigrants are functionally and phenotypically mature, and the purported greater maturity of medullary relative to cortical thymocytes is often cited a evidence for the medullary origin of thymic emigrants, a suggestion not without its critics. To approach this question, we have now isolated a a subpopulation of thymocytes expressing high levels of a receptor that mediates the homing of blood-borne lymphocytes into peripheral lymph nodes. Surprisingly, this population of cells (1-3% of total thymocytes) is both cortical and immunocompetent, containing approximately half of all thymic cytolytic T-lymphocyte precursors. The combination of homing receptor expression and immunocompetence makes this cortical population ideally suited for emigration to peripheral lymphoid organs.     

Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG

Rheumatoid arthritis (RA) is a widely prevalent (1-3%) chronic systemic disease thought to have an autoimmune component; both humoral and cellular mechanisms have been implicated. Primary osteoarthritis (OA) is considered to be distinct from rheumatoid arthritis, and here damage is thought to be secondary to cartilage degeneration. In rheumatoid arthritis, immune complexes are present that consist exclusively of immunoglobulin, implying that this is both the 'antibody' (rheumatoid factor [RF]) and the 'antigen' (most commonly IgG). Autoantigenic reactivity has been localized to the constant-region (C gamma 2) domains of IgG. There is no evidence for a polypeptide determinant but carbohydrate changes have been reported. We have therefore conducted a study, simultaneously in Oxford and Tokyo, to compare in detail the N-glycosylation pattern of serum IgG (Fig. 1) isolated from normal individuals and from patients with either primary osteoarthritis or rheumatoid arthritis. The results, which required an evaluation of the primary sequences of approximately 1,400 oligosaccharides from 46 IgG samples, indicate that: (1) IgG isolated from normal individuals, patients with RA and patients with OA contains different distributions of asparagine-linked bi-antennary complex-type oligosaccharide structures, (2) in neither disease is the IgG associated with novel oligosaccharide structures, but the observed differences are due to changes in the relative extent of galactosylation compared with normal individuals. This change results in a 'shift' in the population of IgG molecules towards those carrying complex oligosaccharides, one or both of whose arms terminate in N-acetylglucosamine. These two arthritides may therefore be glycosylation diseases, reflecting changes in the intracellular processing, or post-secretory degradation of N-linked oligosaccharides.     

Genes for the major protein antigens of the leprosy parasite Mycobacterium leprae

Leprosy, a chronic infectious disease afflicting between 10 and 15 million people, is caused by the obligate intracellular parasite Mycobacterium leprae. Although M. leprae was the first identified bacterial pathogen of man, basic biochemical, immunological, diagnostic and therapeutic investigations have been severely limited because it remains one of the few human pathogens that have not been cultured in vitro. An M. leprae recombinant DNA expression library was constructed to provide a source of genes encoding proteins relevant for such studies. Monoclonal antibodies directed against M. leprae specific antigens have been used to isolate the genes encoding the five most immunogenic protein antigens of the leprosy bacillus. We report here that M. leprae specific epitopes recognized by all of 13 monoclonal antibodies tested were produced by recombinant phage in Escherichia coli.