ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02817.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Recent molecular cloning studies have revealed that some autoantibodies may be encoded directly by germline Ig variable (V) genes without any somatic mutation, suggesting strongly that such autoantibodies are physiologically important. Independent analyses of Ig gene expression in a human fetal liver showed that only nine heavy chain V (Vh) genes were used, out of a potential germline Vh gene repertoire of 100–200. We have observed that four of these nine Vh genes encode sequences identical or almost identical to human autoantibody heavy chains. This unexpected overlap implies that some autoantibodies are expressed preferentially during early development. Recent structural analyses of two Vh3 genes expressed in fetal liver revealed many more enhancer‐like sequences in the fianking regions than expected for a typical Vh gene. It is hypothesized that these autoantibody‐related Vh genes may contain various combinations ofcisregulatory elements which infiuence their specific expression during early ontogenic development. Furthermore, these observations are consistent with network hypotheses, which suggest that early B‐cell development is driven by reactivity with self. Thecisregulatory elements in the autoantibody genes may act in concert with the positional effects that have been shown to facilitate Vh gene eng

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02818.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

In the present study the clearance kinetics and tissue distribution of aggregated125I‐labclled monoclonal rat IgA ([125I] AIgA) of different sizes were studied in rats. Soluble [125I]AIgA disappeared from the circulation in a biphasic manner with an initial rapid distribution half‐life (TI) and a second slower half‐life (T2).T2 was directly related to the size of the aggregates. High molecular weight [125I]AIgA, containing 10–12 IgA molecules per aggregate ([lgA]10–12). was cleared much faster than low molecular weight aggregates. The main site of clearance was the liver. The larger the size of the AIgA, the more degradation products were found in the circulation. After injection of [[lgA]10–12, non‐parenchymal cells (NPC) contained three times more radioactivity than parenchymal cells(PC)(NPC:P ratio 3.06 ± 0.96). Ratios of 0.82 ± 0.0.3 and 0.62 ± 0.12 were observed when [IgA]5–6and [IgA]2were injected respectively, suggesting a greater role for Kupffer cells in the clearance of large‐sized IgA aggregates. Kupffer cells were shown to be the main cells for localization of large‐sized AIgA established by immunohistochemical staining on l

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02819.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The presence of receptors for oestradiol‐17β and 5α‐dihydrotestosterone(5α‐DHT) in the human monocytic leukaemia cell line JIII and rat peritoneal macrophages was investigated using whole‐cell assays. For both cell types. high‐affinity binding species for oestrogen were detected, whereas no indication of specific binding was observed for 5α‐DHT. Analysis of the data according to Scatchard showed curved lines, indicating the presence of two different oestrogen‐binding species. The dissociation constant (Kd) values for the receptors of the rat peritoneal maorophages were calculated to be 1.4 × 10‐10M and 3.3 × 10‐9M, while for the JIII cells, the Kdvalues were 8.7 × 10‐11M and 2.5 × 10‐9M. Sucrose‐gradient ultracentrifugation identified one oestrogenbinding species or 7.IS. The receptors had a relatively high affinity for diethylstilboestrol (DES) but did not bind to a monoelonal antibody specific for the classical oestrogen receptor, suggesting that oestrogen receptors in macrophag

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02820.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Haemopoietic cells carry a variety of cell‐surface molecules, some of which are known to have allotypic variation. In rats, the RT7 alloantigenic system has been well documented using alloantisera. We have produced the first mouse hybridomn cell line secreting an antibody. H1S41, which binds to leucocytes of rat strains carrying the RT7.2 but not the RT7.1 determinant. An lgG2b isotype switch variant (HIS4l.2b) of the original HIS41 (IgG1 isotype) was also made. HIS41 showed a clear and discrete binding in immunofluorescenl and histological experiments and has already been used in several studies on haemopoietic cell turnover and differentiation employing PVG rats congenic for RT7. The present study addresses the question of whether the RT7 gene products are members of the L‐CA family, which has been a matter of controversy over the last decade. When using HIS41 for the analysis of tissue distribution and molecular weight of RT7 gene products, a strong similarity was evident with the data reported for the L‐CA detected by MRC OX‐1 and MRC OX‐30. These two MoAb have been reported to bind to all members of the L‐CA family. All haemopoietic cells, excluding erythrocytes and the more mature stages of erythropoiesis, stained with HIS41. The molecular weights of HIS41 binding molecules on thymocytes and peripheral T cells were comparable to the L‐CA precipitated by MRC OX‐1. Capping and sequential immunoprecipitation studies indicated that HIS41 and MRC OX‐30‐ binding molecules were identical. MRC OX‐1. however, appeared to bind only a subset of these molecules. Thus, our study confirms the identity of RT7.2 gene products and L‐CA. lt also revealed a difference between MRC OX‐1 and MRC OX

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02821.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Subclasses of IgG antibodies to pneumococcal polysaccharide serotypc antigens 4, 6A. and 23F were measured before and 4 weeks after vaccination with pneumoeoccal vaccine in young individuals splencetomized because of trautna and in a control group. An ELISA technique was applied. IgG2 anti‐pneuniococcal antibodies predominated before vaccination, especially against serotypes 4 anti 6A. The youngest individuals in the splenectomy group tended to have lower IgG2 antl‐pneumococcal antibody levels than the older ones. Vaccination induced antibodies of the IgGl and IgG2 subclasses, and in sotne individuals also of the IgG4 subclass. Splencetomy does not seem to inffuence the IgG subcllass paltern of antipneuniococcal antibod

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02822.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The potential of activaied HLA class II‐positive T cells as anligen‐/alloantigen‐presenting cells remains controversial. In our model system we use in vitro‐primed. HLA class II‐specitic T cells of the memory T‐cell phenotype, CD4+. CD29+(4B4+), and CD45RO+(UCHL‐1), We have previously shown that alloactivated. HLA class II‐posilive T cells (Ta) are unable to stimulate proliferalive responses in naive and primed allospecific T cells when ‘back‐stimulation’ is avoided. The explanation of this feature of Ta is unknown, but it is due neither to suppression nor to insufficient HLA class II expression. Accordingly, we investigated the possibility that Ta have a deficient expression of accessory signals critical for the induction of proliferative T‐cell responses. We found that (I) non‐mitogenic concentrations of phorbol myristate acetale (PMA) in combination with either rIL‐4, a CD28‐reaclive MoAb (Kolt‐2). or a calcium ionophore (A23187) enabled Ta to elicit alloantigen‐specific memory T‐cell responses and to present purified protein derivative (PPD) to PPD‐speciftc T‐cell lines. The addition of irradiated, Epstein–Barr virus‐transformed B‐cell lines (EBV‐LCL) (but not their supernatants) had a similar but less pronounced effcet; (2) MoAb directed against HLA class II, CD25 (IL‐2R), CD2, CD4, CD11a (LFA‐1), or CD45RO molecules inhibited these responses; (3) PMA was required within the first hour of culture in order to induce optimal alloantigen‐specifie T‐cell aetivation. while rIL‐4 was fully effective when added after 20–44 h of culture; (4) incubation for 20 h of Ta with rIL‐4 plus PMA markedly up‐regulated CD54 expression on the Ta, and IL‐4 seemed to potentiate the effect of PMA on the CD54 expression. In conclussion, the present data indicate that the inability of Ta to elicit (allo)antigen‐speciffe, proliferative T‐cell response is due to a lack of critical accessory signals. Up‐regulation of CD54 was not sufficient for Ta to stimulate proliferative responses. Neither cytokines (IL‐1, IL‐6, and others) nor triggering of CD2 epitopes (T11.2 and T11.3) by soluble MoAb or solid phase support by MoAb against a number of accessory molecules provided the necessary signals. Thus, our data indicate that other, as yet unknown, signalling pathways play a key role in antigen‐ and allo

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02823.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Chronic schistosomiasis mansoni is associated with impaired cell‐mediated immune responsiveness (CMI). To assess co‐stimulatory factors essential in the induction phase of CMI, interleukin 1 (IL‐1) concentration was determined in the sera and cell culture supernatants ofSchistosoma mansoni‐infected patients, and circulating monocytes were phenotyped, labelling membrane IL‐1 and HLA‐DP. In addition, adherent cell oxidative‐burst capacity was investigated. Since involvement of IL‐1β in the pathogenesis of severe granulomatous lesions could not be ruled out, 17 patients with intestinal schistosomiasis and 17 patients with hepatosplenic schistosomiasis were matched for intensity of infection and monitored 3–6 months after praziquantel therapy. Seventeen age‐ and sex‐matched uninfected residents ofthe study area in Alagoas, Brazil, acted as controls. Whereas schistosomiasis patients and controls did not differ in the expression of monoeyte surface antigens and the capacity of adherent cells to generate H2O2, IL‐1β release by monocytes in vitro was significantly reduced in both intestinal and hepatosplenic patients. Low concentrations of circulating IL‐1β were detected in comparable frequencies in untreated patients and controls. Three months after therapy, IL‐Iβ was detectable in serum in an increased proportion of intestinal schistosomiasis patients. IL‐1 release in vitro gradually increased in all patients and reached cont

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02824.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Controversy has existed as to the ability of leukotriene B4(LTB4) to enhance adhesive properties of human neutrophils (PMN) and endothelial cells. We found that LTB4 induced a rapid but transient adhesion of PMN to an albumin‐coated plastic surface and to cultured human umbilical vein endothelial cells (HUVEC). Although the adhesive response of PMN to the chemotactic peptideN‐formyl‐methionyl‐leucyl‐phenylalaninc (fMLP) was longer lasting, peak hyperadherence was of similar magnitude as to LTB4 and was less susceptible to assay conditions. Adherence induced by either LTB4 or fMLP could be abrogated by the monoclonal antibody 60.3, indicating similar dependence on the leucocyte adhesion protein CD18. Lipoxin A did not induce PMN hyperadherenee. Treating HUVEC with LTB4, but not with its omega‐oxidized metabolites 20‐OH‐ and 20‐COOH‐LTB4, lipoxin A, or with IMLP conferred a rapid, dose‐related, enhanced adhesion of PMN. This effect was dependent on CD18 and on divalent cations. It disappeared with prolonged exposure to LTB4, required a metabolically active HUVEC, and was not due to passive binding of LTB4 lo HUVEC. Thus, LTB4 induces a transient expression of hyperadhesiveness in HUVEC as well as in neutrophils, and both effects are dependent

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02825.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Mice were immunized against fiuorescein isothiocyanate (FITC)‐labelled human gamma globulin (HGG) or dexlran sulphate (DXS) in the absenee or presence of different adjuvants. The immune response was assayed as the total Ig‐secreting cells and FITC‐speeilic plaque‐forming cells (PFC) found in various lymphoid organs. The adjuvants inliueneed the isolype of antibodies produced to the same antigenic determinant. The PFC of different IgG subclasses were favoured by different adjuvants. The IgG3 isotype was produecd mainly alter immunization with either anligen and lipopolysaccharide(LPS)or Li sail asadjusani; IgGI was produced with incomplete Feund's adjuvant (IFA), complete Freund's adjuvani (CFA), alum, poly I:C. Quil A, Be salt, and poly A:U. Some of the above adjuvanis (Be salt and poly A:U) favoured the production of lgG2b, and others (CFA, alum. Quil A, and poly I:C) favoured ihe IgG2a isotype besides the main isotype. Attempts were made to correlate the activation by the various adjuvants of certain THsubtypes with the isotypes p

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02826.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY