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1. |
Twenty years into the saga of MHC‐restriction |
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Australian Journal of Experimental Biology and Medical Science,
Volume 72,
Issue 6,
2017,
Page 447-454
GORDON ADA,
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摘要:
SummaryTwenty years ago, the terms ‘altered self and ‘H‐2 restriction’, later modified to ‘MHC‐restriction’, were coined to describe the finding by Peter Doherty and Rolf Zinkernagel that murine cytotoxic T cells (CTL) would lyse virus‐infected target cells only if effector and target cells were H‐2 compatible. This short review recalls those heady days and briefly recounts some of the later findings in three aspects of particular interest raised by the original finding: the nature of the T cell receptor, the composition and structure of the ligand on the target cell recognized by the TCR, and the importance of CTL in the control and clearance of infections in general.
ISSN:0004-945X
DOI:10.1038/icb.1994.68
出版商:Blackwell Publishing Ltd
年代:2017
数据来源: WILEY
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2. |
HLA‐A incompatibility associated with enhanced long‐term renal graft survival in HLA‐B, DR mismatched transplants |
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Australian Journal of Experimental Biology and Medical Science,
Volume 72,
Issue 6,
2017,
Page 455-460
D. BUĆIN,
H. EKBERG,
A. LINDHOLM,
H. PERSSON,
G. TUFVESON,
D. ALBRECHTSEN,
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摘要:
SummaryThe effect of HLA‐A matching on long‐term cadaver kidney graft survival was analysed, on average, 6 years after transplantation in a total of 1085 cyclosporine (CyA)‐treated patients.A beneficial effect of HLA‐A mismatching on graft survival was found by univariate and multivariate analyses (P<0.05).Enhanced graft survival was associated with HLA‐A mismatching in transplants mismatched for HLA‐B,DR (P= 0.03), but not in HLA‐B,DR compatible transplants.High 6 year graft survival rates, 78% and 66%, were found in transplants mismatched for two or one HLA‐A antigens, respectively, among patients without any acute rejection episode. This was significantly higher than the survival rate of 55% found in HLA‐A compatible transplants (P= 0.001). In patients who had suffered from acute rejection episodes, a prolonged graft survival was also associated with HLA‐A mismatching in HLA‐B,DR mismatched transplants (P= 0.04).The beneficial effect on graft survival of HLA‐A mismatching was most pronounced in patients treated with high/medium dose CyA and prednisolone (P=0.004 overall andP= 0.0007 for HLA‐B,DR mismatched transplants).In conclusion, HLA‐A mismatching was associated with enhanced long‐term renal graft survival in CyA‐treated recipients of HLA‐B,DR mismatched transplants. In clinical situations, the present results might, if confirmed, contribute to the prolongation of long‐term graft survival. The results might indicate the existence of tolerance promoting allogeneic markers within the HLA‐A class I region.
ISSN:0004-945X
DOI:10.1038/icb.1994.69
出版商:Blackwell Publishing Ltd
年代:2017
数据来源: WILEY
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3. |
Regulation of C3 deposition on gp120 coated CD4 positive cells by decay accelerating factor and factor H |
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Australian Journal of Experimental Biology and Medical Science,
Volume 72,
Issue 6,
2017,
Page 461-470
T. A. SADLON,
S. J. PARKER,
D. L. GORDON,
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摘要:
SummaryWe investigated complement activation by recombinant gp120 (rgp120) treated CD4 cells and the role host complement regulatory proteins play in controlling C3 deposition. Complement activation was determined by detection of C3 on rgp 120 coated cells in the presence and absence of HIV seropositive sera using flow cytometry. Treatment of rgp 120 coated cells with complement resulted in C3 deposition only if HIV positive sera was included. Examination of C3 fragments on these cells demonstrated rapid cleavage of C3b to iC3b. The role of the regulatory proteins was examined by pretreating cells with mAb to block decay accelerating factor (DAF) or membrane cofactor protein (MCP) or by using factor H depleted sera as a complement source. Inhibition of DAF or use of factor H depleted sera significantly increased C3 deposition on rgp120 coated cells. In contrast, C3 deposition on rgp120 coated cells was not increased after blocking MCP. The sensitivity of rgp120 coated cells to complement lysis was unchanged after inhibition of the regulatory proteins, despite the increase in C3 deposited. These results indicate that in a model of virus infected cells, C3 deposition is regulated by DAF and factor H but MCP appears to have no role.
ISSN:0004-945X
DOI:10.1038/icb.1994.70
出版商:Blackwell Publishing Ltd
年代:2017
数据来源: WILEY
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4. |
β2Integrin independent neutrophil recruitment and injury in anti‐GBM glomerulonephritis in rabbits |
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Australian Journal of Experimental Biology and Medical Science,
Volume 72,
Issue 6,
2017,
Page 471-479
P. G. TIPPING,
L. J. CORNTHWAITE,
S. R. HOLDSWORTH,
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摘要:
SummaryThe role of the β2 integrin cell adhesion molecules (CAM) in directing neutrophil accumulation and injury in acute anti‐glomerular basement membrane antibody induced glomerulonephritis (anti‐GBM GN) was assessed in rabbits byin vivoinhibition of CD 18 dependent neutrophil/endothelial cell interactions using a monoclonal anti‐CD 18 antibody. Rabbits given horse anti‐rabbit GBM antibody developed significant glomerular neutrophil influx (2.9 ± 0.1 neutrophils per glomerular cross‐section [c/gcs], normal 0.1 ± 0.1 c/gcs,P= 0.002) and proteinuria (1389 ± 257 mg/16 h, normal 15± 4mg/16 h,P= 0.0015) after 16 h. Rabbits rendered neutropenic (<500 neutrophils/μL) by mustine hydrochloride, or complement depleted by cobra venom factor, did not develop glomerular neutrophil accumulation and had markedly reduced proteinuria after anti‐GBM antibody, demonstrating complement‐induced neutrophil recruitment is a major mechanism of glomerular injury in this model. Anti‐CD 18 antibody treatment of rabbits developing anti‐GBM GN abrogated dermal neutrophil influx in response to intradermal injection of fMLP and zymosan activated serum. Treated rabbits achieved levels of anti‐CD 18 antibody in their serum which saturated the binding sites on rabbit neutrophilsin vitro, and their circulating neutrophils had saturated anti‐CD 18 antibody bindingin vivo.However, glomerular neutrophil influx (3.5 ± 0.4 c/gcs) and proteinuria (1210 ± 428 mg/16 h) were both unaffected. Thus, in this model of antibody‐initiated complement and neutrophil‐dependent glomerular injury, in which neutrophil transmigration across the endothelium is not required, effective functional inhibition of β2integrin CAMin vivodid not reduce glomerular injury or glomerular neutrophil influx. These studies demonstrate that β2integrin CAM are not a requirement for neutrophil accumulation and glomerular injury in anti‐GBM GN in rabbits.
ISSN:0004-945X
DOI:10.1038/icb.1994.71
出版商:Blackwell Publishing Ltd
年代:2017
数据来源: WILEY
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5. |
Internalization of the anticoagulant thrombomodulin is constitutive and does not require a signal in the cytoplasmic domain |
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Australian Journal of Experimental Biology and Medical Science,
Volume 72,
Issue 6,
2017,
Page 480-488
M. S. TEASDALE,
C. H. BIRD,
P. BIRD,
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摘要:
SummaryEndocytosis of the protein C activation cofactor thrombomodulin (TM) is thought to be induced by interaction of TM with its ligand, thrombin, or by the action of inflammatory cytokines on endothelial cells. To examine the internalization of TM in the absence of thrombin or cytokines we used two assays. The first was a two‐colour indirect immunofluorescence technique to simultaneously monitor cell surface and internal pools of TM. The second involved labelling a cell surface pool of TM and following its cellular redistribution over time. Using these techniques we demonstrated that in both TM‐transfected COS cells and in endothelial cells, TM internalizes constitutively. Removal of the cytoplasmic domain, which in most receptors contains the internalization signal, did not abolish TM internalization. These results suggest that endocytosis of TM does not occur via coated pits, and that internalization probably is not a significant cause of the endothelial TM loss associated with several pathological states.
ISSN:0004-945X
DOI:10.1038/icb.1994.72
出版商:Blackwell Publishing Ltd
年代:2017
数据来源: WILEY
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6. |
Lack of correlation between early intracellular calcium ion rises and the onset of apoptosis in thymocytes |
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Australian Journal of Experimental Biology and Medical Science,
Volume 72,
Issue 6,
2017,
Page 489-499
JOANNE P. BEAVER,
PAUL WARING,
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摘要:
SummaryApoptosis, a well‐recognized process of cell death, is usually defined by chromatin condensation, plasma membrane blebbing, reduction in cell volume, and in many cell types the cleavage of DNA into nucleosomal multiples, and finally the formation of apoptotic bodies. We have characterized the time of onset and the range of concentrations at which the toxins gliotoxin and thapsigargin induce apoptosis in thymocytes. We also looked for early changes in cytosolic calcium ion concentration ([Ca‐2+]i). Three methods were used to detect apoptosis: cellular morphology, DNA fragmentation and a flow cytometric method using ethidium bromide. Calcium fluxes were measured using both flow cytometry and bulk cell fluorimetry. Gliotoxin concentrations of 50 nmol/L to 10μmol/L induced significant numbers of cells to become apoptotic in a dose dependent manner. At these concentrations there was no observable increase in [Ca2+]ias determined by flow cytometry or in bulk cells. However, when thymocytes were treated with gliotoxin at concentrations greater than 500 μmol/L, rises in [Ca‐2+]iwere apparent, but these cells died by necrosis. Thapsigargin induced low levels of apoptosis in thymocytes; the maximum effect observable after a 10 nmol/L treatment. Thapsigargin is known to inhibit the Ca2+‐ATPase in the endoplasmic reticulum thereby causing a sustained increase in [Ca2+]iin thymocytes. The rise in [Ca2+]iobserved was quantitatively similar when thymocytes were treated with thapsigargin concentrations ranging between 10 and 100 nmol/L. These results led us to investigate the effect of dexamethasone on [Ca2+]i, In these experiments thymocytes showed no rises in [Ca2+]iabove the control over 85 min following treatment with 10 μmol/L dexamethasone.
ISSN:0004-945X
DOI:10.1038/icb.1994.73
出版商:Blackwell Publishing Ltd
年代:2017
数据来源: WILEY
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7. |
Differential expression of CD45R0 on natural killer (NK) cells in patients with an NK lymphocytosis |
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Australian Journal of Experimental Biology and Medical Science,
Volume 72,
Issue 6,
2017,
Page 500-507
HILARY S. WARREN,
BEVERLEY F. KINNEAR,
LOUISE J. SKIPSEY,
RICHARD G. PEMBREY,
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摘要:
SummaryNK cells from three donors with a NK (CD3−CD56+CD 16+) lymphocytosis of unknown aetiology showed differential expression of CD45R0, an isoform of CD45 not expressed by NK cells from normal donors unless stimulated to proliferatein vitro.For donor FC, 60% of NK cells expressed CD45R0 over a 16 month period during which there was a partial resolution of the NK lymphocytosis. For donor SW, 37% of NK cells expressed CD45R0, increasing to 87% over a 14 month period during which the NK lymphocytosis increased. For donor RN few if any NK cells expressed CD45R0. Afterin vitroproliferation, 100% of NK cells generated from all donors expressed CD45R0. For donors FC and SW, CD45R0 remained expressed on more than 90% of cells at 3–4 weeks following cessation of proliferation. By contrast CD45R0 expression was gradually lost during long‐term culture of NK cells from donor RN, with 58% of NK cells regaining the pre‐culture CD45R0‐phenotype. NK cells from normal donors also varied in the extent to which activation acquired CD45R0 was lost during long‐term culture. The results obtained are consistent with the notion that NK cells from the NK lymphocytosis donors studied have previously undergone proliferationin vivo.
ISSN:0004-945X
DOI:10.1038/icb.1994.74
出版商:Blackwell Publishing Ltd
年代:2017
数据来源: WILEY
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8. |
Do lymphocytes require calibration? |
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Australian Journal of Experimental Biology and Medical Science,
Volume 72,
Issue 6,
2017,
Page 508-512
NICHOLAS R. Stc. SINCLAIR,
COLIN C. ANDERSON,
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摘要:
SummaryComplexity in the activation/regulatory apparatus and the variable nature of the antigen‐binding site dictate that B and T cells establish and select, during their development, appropriate activation and control mechanisms beyond simple antigen‐binding specificity. These mechanisms are established partly by fixed interactions dictated by genetically defined structures, but they are also attained by calibration during ontogeny. This calibration depends on the ordered expression of early components (each of which is invariant), on their interaction with specific ligands, and on the receipt of invariant signals for calibration. Lymphocytes calibrate themselves by expressing various cell surface components, such as restricted heavy chain D‐regions and pseudo‐light chains. These are expressed in association with elements that will make up the antigen‐receptor complex of mature lymphocytes. Calibration by invariant signals results in the establishment, selection and active maintenance of cellular activities which serve to control lymphocyte function. Since these cellular activities are one of a number of possible conditions, they are referred to as variant controls. Effectively calibrated basic cellular functions, specialized responses and cellular interactions allow lymphocytes to attain self‐nonself discrimination. If calibration fails, lymphocytes will develop abnormalities, such as immunodeficiency and autoimmunity.
ISSN:0004-945X
DOI:10.1038/icb.1994.75
出版商:Blackwell Publishing Ltd
年代:2017
数据来源: WILEY
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9. |
Novel structural features of autoantibodies in murine lupus: A possible superantigen binding site? |
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Australian Journal of Experimental Biology and Medical Science,
Volume 72,
Issue 6,
2017,
Page 513-520
D. JESKE ZACK,
A. L. WONG,
R. H. WEISBART,
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摘要:
SummaryThe stimulus for the production of anti‐DNA autoantibodies in lupus remains unknown. Since double‐stranded DNA (dsDNA) is a weak immunogen, other stimuli such as B cell superantigens or anti‐idiotypic antibodies may provide an alternative mechanism for their production. The presence of regulatory determinants on autoantibodies might be revealed through their structural characterization, but they have eluded detection, perhaps because they may be three‐dimensional and require closer analysis. In this report we cloned and sequenced the heavy chain variable region (VH) of a monoclonal anti‐dsDNA antibody, mAb 3E10, derived from MRL/lpr mice with lupus nephritis previously shown to express an idiotype associated with nephritis in murine and human lupus. We now show that mAb 3E10 VH contains novel structural features unrelated to DNA binding which are shared only by a subset of autoantibodies expressed in murine lupus. These lupus autoantibodies can be distinguished from antibodies of non‐autoimmune strains by the presence of a specific sequence at the junction of the diversity and joining genes combined with the use of variable region genes with conserved sequences in framework 1 (FRl) and FR3. The location of the novel sequences indicates the possibility of a three‐dimensional solvent‐exposed determinant located distant from the classical antigen binding site that could regulate their production, possibly through binding B cell superantigens or other infectious agents.
ISSN:0004-945X
DOI:10.1038/icb.1994.76
出版商:Blackwell Publishing Ltd
年代:2017
数据来源: WILEY
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10. |
Book Reviews |
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Australian Journal of Experimental Biology and Medical Science,
Volume 72,
Issue 6,
2017,
Page 521-522
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摘要:
Book Reviewed in this article:METHODS OF IMMUNOLOGICAL ANALYSIS. Volume IIIEdited by R. F. Masseyeff, W. H. Albert and N. A. Staines.MACROPHAGE‐PATHOGEN INTERACIIONSEdited by B. S. Zwilling and T. K. Eisenstein
ISSN:0004-945X
DOI:10.1038/icb.1994.77
出版商:Blackwell Publishing Ltd
年代:2017
数据来源: WILEY
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