The triggering of the TCR/CD3 complex by anti-CD3 (OKT3) antibody leads to the formation of T cell clusters. In cultures of T lymphocytes from most normal individuals, the peak of cluster formation occurs at 24 h, but with cells from patients with common variable immunodeficiency (CVI) it was seen earlier at 4-9 h; in addition, the clusters were larger than normal, particularly at 9 h. Cluster formation by CVI and normal cells was dependent on temperature and divalent cations, but did not require Fc receptors. Since OKT3 clustering is known to be dependent on the LFA-1/ICAM-1 adhesion system, the effect of monoclonal antibodies directed against these molecules was tested. A potent inhibitor was the antibody against the common beta chain of the integrin family (CD18), but of four MoAbs against the alpha chains (CD11), three inhibited and one stimulated T cell aggregate formation. Increased expression of LFA-1 or ICAM-1 on CVI patients' T cells could not be demonstrated. The accelerated clustering was therefore probably due to an increase in the proportion of cells carrying the activated form of LFA-1. The formation of large numbers of homotypic lymphocyte clusters might reduce the effective interaction between B and T cells, thus contributing to the depression of immunoglobulin synthesis observed in this disease. 相似文献
The association of rheumatoid arthritis (RA) with particular MHC class II genes suggests that autoantigen-spccific T cell clones present in joints could be central to the pathogenesis of the disease. Previous investigations on the clonal diversity of T cells infiltrating the rheumatoid synovial membrane have yielded conflicting results. With the use of Southern blot analysis, we investigated the clonalily of rheumatoid T cell lines expanded from peripheral blood, synovial fluid and synovial tissue. From peripheral blood lymphocyte (PBL) of RA patients and healthy normal controls, we also checked the consequences of two different culture conditions on the clonality of these cell lines. From control PBL, we found that in vitro non-specific expansion of non-clonal T cell populations does not create artefactual clonal selection. However, growing T cells in ritro with IL-2 seems to be able to lead to preferential expansion of cells bearing IL-2 receptor (IL-2R). We identified such in vivo activated IL-2-sensitive T cell clones frequently in RA synovial tissue (8/13) and more rarely in synovial fluid and peripheral blood (3/12). One patient presents the same T cell receptor gene rearrangements in synovial membrane of two affected joints. In RA synovial tissue, the frequency of these IL-2-responsive T cells is most prevalent among actively inflamed membranes removed early in the disease process. The role and the relevance to the disease of these I L-2-responsivc T cells remain to be elucidated. 相似文献
The expression of receptors for complement and the Fc region of immunoglobulin by alveolar macrophages (AM) constitutes a valuable aid to effector function of these cells. However, during HIV infection such expression may also act to increase binding of immune complexes, thus facilitating viral infection of these cells. This study was designed to determine whether changes in the expression of these receptors occurs in situ during HIV infection. Lung macrophages were isolated by bronchoalveolar lavage in groups of HIV+ subjects segregated on the basis of peripheral CD4 count. A group of normal subjects was also investigated. Expression of CR1 and FcγRI was quantified by measuring the optical density of reaction product following controlled immunoperoxidase staining with MoAbs CD35 and CD64. Both CR1 and FcγRI were increased over normal in all HIV+ subjects. This increase was progressive with advancing disease as determined by correlation with declining peripheral CD4 count. Comparison of asymptomatic and symptomatic subjects with HIV infection showed no difference in CR1 expression but a rise in FcγRI expression in the latter group. An overall inverse correlation was also found between peripheral CD4 count and FcγRI expression, but not CR1 expression. These data demonstrate a significant increase in the expression of these receptors on AM from HIV+ subjects, and show that this increase may occur before any symptoms in these patients. 相似文献
The aim of the study was to test the hypothesis that baroreceptor unloading increases jejunal fluid absorption rate via an α2-adrenergic effect on electrogenic active transport. In 13 chloralose-anaesthetized cats, the carotid sinus baroreceptors were isolated and perfused with arterial blood, and we studied the effects of a graded decrease in carotid sinus pressure on intestinal vascular resistance, net fluid absorption rate and the potential difference between the intestinal lumen and the peritoneal cavity (PD). Experiments were performed in seven control animals and in six animals pretreated with yohimbine, an α2-adrenergic antagonist, at a dose of 0.1 mg kg-I i.v. Yohimbine per se had no significant effects on systemic arterial pressure, intestinal vascular resistance, net fluid absorption rate or PD. In the control animals, baroreceptor unloading induced an increase in systemic arterial pressure, intestinal vascular resistance and net fluid absorption rate, and a decrease in the PD. Yohimbine pretreatment did not significantly affect the systemic blood pressure response to baroreceptor unloading, but abolished the effect on intestinal vascular resistance and PD. After yohimbine treatment, decreases in carotid sinus pressure still enhanced net fluid absorption rate, but this response was observed in a higher range of carotid sinus pressures than in control animals. We conclude that (1) a major component of the increase in jejunal absorption rate during baroreceptor unloading is due to a non-electrogenic mechanism, which may be either active or passive; (2) this component of the response is not blocked by yohimbine at a dose sufficient for an effect on presynaptic α2-receptors; (3) the absorptive response to baroreceptor unloading is not a phenomenon secondary to the concomitant jejunal vasoconstriction. 相似文献
The Thy-1 antigens or rat brain and thymus have been isolated and chemically characterized, but those of mice have not been identified. Moreover, it is uncertain whether the antigens are glycolipids or glycoproteins. This study with highly purified preparations of gangliosides GM1, 1GD1a, GD1b and GT1b from bovine brain and several ganglioside fractions from mouse brain showed that Thy-1 activity does not reside in gangliosides, but rather in the chloroform-methanol-insoluble residue of brain remaining after extraction of gangliosides. The antigen could be solubilized from this residue with a non-ionic detergent. The antigenic activity of the solubilized preparation was heat-labile but resistant to periodate. The chemical properties of the Thy-1 antigen of mouse brain are discussed. 相似文献
This study presents a comparative analysis of gangliosides from lymphoid (spleen and thymus) and other (brain, liver, lungs and muscle) tissues of C57BL/6 mice lacking the gene for beta2-microglobulin (beta2M), a constitutive component of the MHC class I molecule. Ganglioside fractions in the tissues of mice homozygous (beta2M-/-) and heterozygous (beta2M-/+) for the gene deletion were determined by high performance thin-layer chromatography (HPTLC), followed by immunostaining with specific polyclonal antibodies. Ubiquitous gangliosides GM3(Neu5Ac) and GM3(Neu5Gc) were the dominant gangliosides in the lungs of the control beta2M-/+ mice, whereas the homozygous knockout mice had substantially decreased expression of these structures. The lungs of the beta2M-/- mice also had reduced expression of T-lymphocyte-specific GM1b-type gangliosides (GM1b and GalNAc-GM1b). beta2M-deficient mice also had more GM1a and GD1a gangliosides in the liver, and several neolacto-series gangliosides were increased in the brain and lungs. This study provides in vivo evidence that the beta2M molecule can influence the acquisition of a distinct ganglioside assembly in different mouse organs, implicating its non-immunological functions. 相似文献
Cell adhesion to the extracellular matrix appears to trigger a cascade of intracellular signalings. We have previously shown
that treatment of ovarian cancer cells, NOM1, with fibronectin (FN) stimulated matrix metalloproteinase (MMP)-9 secretion
and thereby activated the invasiveness of cells via the FAK/Ras signaling pathway. By use of chemical inhibitors, we investigated
the downstream effectors critical for FN-dependent secretion of MMP-9. Treatment of cells with MEK1 inhibitors, U0126 and
PD98059, dramatically suppressed the secretion of MMP-9 activated by FN. Similarly, PI-3 kinase inhibitors, Wortmannin and
LY294002, strongly suppressed the FN-dependent secretion of MMP-9 together with the inhibition of Akt activation. In contrast,
a specific PKC inhibitor (GF109203X) showed no inhibitory effect on the FN-dependent MMP-9 secretion. Moreover, we found that
both the MEK1 inhibitor and the PI3-K inhibitor, but not the PKC inhibitor, strongly suppressed the invasiveness of NOM1 cells.
Taken together, our results suggest that activation of dual signaling pathways, MEK1-MAPK and PI3K-Akt, is required for the
FN-dependent activation of MMP-9 secretion. Our results suggest the importance of these signaling molecules as a chemotherapeutic
target for cancer.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
Summary: Blends of high molecular weight poly(R‐3‐hydroxybutyrate) (PHB) ( = 352 000 g · mol?1), comprising of either low molecular weight poly(R‐3‐hydroxybutyrate) (D‐PHB) ( = 3 900 g · mol?1) or poly[(R‐3‐hydroxybutyrate)‐co‐(R‐3‐hydroxyvalerate)] (PHBV) ( = 238 000 g · mol?1) with 12 mol‐% hydroxyvalerate (HV) content as a second constituent, were investigated along with the thermal properties and morphologies. After isothermal crystallization, a lowering of the melting temperature of PHB can be observed with increasing content of the second component in the blends. This behavior points towards miscibility of the constituents both in the liquid and the solid state. Crystallization kinetics was studied under isothermal and non‐isothermal conditions. The overall kinetics of isothermal crystallization was analyzed in terms of the Avrami equation. Only one crystallization peak is observed in all cases for the PHB/D‐PHB and PHB/PHBV blends under the conditions studied. This demonstrates co‐crystallization of the constituents. The addition of D‐PHB or PHBV to PHB reduces the rate of crystallization of the blends compared to that of neat PHB. The corresponding activation energies of crystallization also decrease with an increasing concentration of the second constituent. Non‐isothermal crystallization, carried out with different cooling rates held constant, is discussed in terms of a quasi‐isothermal approach. The corresponding rate constants as functions of reciprocal undercooling show Arrhenius‐like behavior in a certain range of temperatures. At sufficiently high undercooling, the rate constants of crystallization for the isothermal process exceed those reflecting non‐isothermal conditions, whereas in the limit of low undercoolings, the rate constants become similar. Ring‐banded morphologies are observed when PHB is in excess. When the respective second component is the major component, fibrous textures of the spherulites develop.