摘要:

AbstractThe heat shock proteins gp96, HSP70, and HSP90 are complexed to a diverse array of cellular proteins and peptides as a consequence of their chaperone functions. There is good experimental evidence that vaccination with these heat shock protein‐peptide complexes elicit immune responses against chaperoned peptide antigens. As shown with gp96, this requires internalization of the heat shock protein‐peptide complexes by macrophages and processing of the chaperoned peptides for class I restricted presentation. Via this process, primarily CD8+antigen‐specific T cells are primed by gp96 vaccination. This might represent a general mechanism for priming of MHC‐class I restricted T cells by professional antigen‐presenting cells. At least gp96 has been shown to be associated with peptides that are not selected by the MHC haplotype of the harboring cell. This allows for immunization with gp96‐peptide complexes across MHC barriers, for example against shared tumor antigens or viral antigens.J. Leukoc. Biol. 60: 153–158; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.2.153

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractThe induction of immediate early genes in cells of the immune system is critical to determining the ultimate outcome of exposure to antigen. The importance of many of these genes relates to the role their transcription factor products play in dictating patterns of expression of downstream, function‐related genes. Evidence from several systems indicates that the immediate early gene,egr‐1 may be of particular importance in the immune system. Recently, theegr‐1 promoter has been shown to be highly responsive to the diverse biochemical signals generated by antigen and cytokines in cells of the immune system. Furthermore, an important role foregr‐1 in determining the differentiation pathway of myeloid cell precursors has been recently elaborated. Finally, potential targets of regulation by the zinc‐finger transcription factor encoded byegr‐1 include the interleukin‐2, CD44, ICAM‐1, and tumor necrosis factor genes. The role ofegr‐1 in regulation of the immune response will be discussed in the context of these recent studies.J. Leukoc. Biol. 60: 159–166; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.2.159

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractWe are investigating neutrophilic infiltration into herpes simplex virus type 1 (HSV‐1) ‐infected mouse corneas. Using a novel ex vivo corneal migration assay, we demonstrated two waves of neutrophil chemotaxis in HSV‐1‐infected corneas. An early chemotactic gradient developed within 48 h in concert with the appearance of HSV‐1 epithelial lesions, peaked by 4 days post‐infection (p.i.), and degraded by 6–8 days p.i. A second chemotactic gradient appeared 10 days after infection, just before the initiation of chronic inflammation. The gradient was maintained in corneas that developed inflammation but rapidly degraded in corneas that failed to develop inflammation. The early chemotactic gradient was established in the absence of T lymphocytes, but the second chemotactic gradient was virtually abrogated by T cell depletion. We conclude that HSV‐1 infection induces two temporally separated neutrophil chemotactic gradients in the mouse cornea: an early, transient, T cell‐independent gradient; and a later, chronic, T cell‐dependent gradient.J. Leukoc. Biol. 60: 167–173; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.2.167

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractTo investigate the effect of type II phospholipase A2(PLA2‐H) on neutrophil function, we assessed the Mac‐1 (CD11b/CD18) expression on human neutrophils by flow cytometry after incubation of the cells with human PLA2‐IL PLA2‐II at a concentration of 10μg/mL increased the Mac‐1 expression by 150% compared with unstimulated cells at 30 min and after. Under these conditions PLA2‐II increased the exocytosis from secretory vesicles but not from azurophilic, specific, or gelatinase granules. The results suggest that PLA2‐II induces translocation of Mac‐1 from the secretory vesicles to the plasma membrane. The Mac‐1 induction mediated by PLA2‐II was inhibited by an anti‐PLA2‐II antibody, which was able to inhibit the catalytic activity. However, the Mac‐1 induction by PLA2‐II was not inhibited by a 5‐lipoxygenase, cyclooxygenase inhibitor, or a platelet‐activating factor antagonist. Thus, we examined the effects of fatty acids and lysophospholipids on Mac‐1 expression. Only arachidonic acid induced Mac‐1 expression. These results imply that PLA2‐II induces Mac‐1 expression on neutrophils via production of arachidonic acid.J. Leukoc. Biol. 60: 174–180; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.2.174

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractDendritic cells (DC), with their potent antigen‐presenting and accessory activities, are involved in the stimulation of naive T cells. To examine the biological functions of DC, we developed a method for generating large numbers of murine splenic DC. First, DC were propagated in vivo by using a granulocyte‐macrophage colony‐stimulating factor‐secreting tumor as a continuous in vivo source of the cytokine. The DC enriched in the spleen, especially in the white pulps, were purified after an overnight culture. We could reproducibly obtain 6 to 10 106splenic DC per mouse. These DC were morphologically similar to interdigitating cells, expressed high levels of MHC class II and costimulatory molecules, and were highly allo‐stimulatory in mixed lymphocyte reactions. Further analysis on T cell stimulation activity revealed that the DC had strong costimulatory activity on human T cells. Activated B cells, which express both B7‐1 and B7‐2, had little T cell costimulatory activity under the same assay conditions. A human histiocytic leukemia cell line, U937, that showed only weak costimulatory activity by itself, worked synergistically with DC and further intensified the T cell stimulation by DC. These findings suggest the presence of a T cell costimulation mechanism in DC, which is activated synergistically by monocytes or macrophages, and deserves further study.J. Leukoc. Biol. 60: 181–190; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.2.181

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractStimulation of the respiratory burst in phagocytes induces the formation of mixed disulfides between sulfhydryl groups of proteins and low‐molecular‐weight thiols. We hypothesized that this process (S‐thiolation) might be involved in turning off the respiratory burst. However, induction of S‐thiolation by pretreatment of neutrophils with diamide, a direct thiol oxidizing agent, actually primed the cells for a two‐ to fivefold increase in total release and fourfold increase in rate of release of O2‐on stimulation by f‐Met‐Leu‐Phe. Generation of intracellular oxidants (hydroethidine fluorescence) was increased ninefold. Priming and S‐thiolation were apparent at 1 min of incubation and peaked at 5–10 min. Diamide pretreatment also reduced the lag time between addition of phorbol diester and release of O2‐by a mean of 23 s (41%). Dithioerythritol, a sulfhydryl‐reducing agent, abolished both the S‐thiolation and priming mediated by diamide. H2O2also induced priming and S‐thiolation; and these were eliminated by dithioerythritol. In contrast to the effect of endotoxin, diamide priming did not affect Ca2+homeostasis of the neutrophils. Diamide did not significantly alter NADPH oxidase activity in a cell‐free system. These findings suggest that sulfhydryl groups on one or more proteins play an important role in modulating the respiratory burst.J. Leukoc. Biol. 60: 191–198; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.2.191

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractEfficient polymorphonuclear neutrophil (PMN) migration depends on specific interactions between PMNs, endothelial cells, and extracellular matrix (ECM) proteins. We investigated the relationship between PMN migration and the ECM molecule fibronectin (FN). We used an in vitro migration assay system to show that human PMNs migrated across an FN‐coated filter barrier toward a formyl‐Met‐Leu‐Phe (fMLP) chemoattractant gradient in greater numbers than across (uncoated) bare filters. In 1 h of fMLP stimulation, 69 ± 6% of the PMNs had migrated across the FN‐coated filters, whereas 46 ± 5% of PMNs migrated across bare filters. This effect was specific to FN; coating the filters with the ECM protein vitronectin did not enhance migration. Monoclonal antibodies against FN or against the α5or β1integrin subunits of the FN receptor inhibited the enhanced PMN migration response across FN‐coated filters. These findings indicate that the extracellular matrix protein FN enhances PMN migration and that this response is mediated by the α5β1FN receptor.J. Leukoc. Biol. 60: 199–206; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.2.199

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractPolymorphonuclear neutrophils (PMNs), traditionally considered effector cells in the inflammatory response, have recently been regarded as potential regulators of the immune response. In the present study we investigate whether PMNs are efficient antigen‐presenting cells for reactivation of memory cytotoxic T lymphocytes (CTLs). PMNs were pulsed with synthetic peptides derived from Epstein‐Barr virus (EBV) antigens. We have used the IVTDFSVIK (IVT) peptide derived from the Epstein‐Barr virus—encoded nuclear antigen 4 protein, corresponding to the immunodominant epitope of HLA‐A11–restricted CTL responses, and the CLGGLLTMV (CLG) peptide derived from the latent membrane protein 2 antigen, representing a subdominant epitope of HLA‐A2–restricted CTL responses. The data indicate that peptide‐pulsed PMNs selectively activate specific CTL responses to both immunodominant and subdominant epitopes. The efficiency of CTL induction by PMNs was comparable to that observed with the conventional method of EBV‐specific CTL reactivation with the autologous lymphoblastoid cell line, as well as with peptide‐pulsed monocyte‐enriched adherent cells. On the contrary, unactivated peptide‐pulsed lymphocytes failed to induce an epitope‐specific CTL response. These results demonstrate that PMNs efficiently present antigens to memory virus‐specific CTLs and suggest that they may have a role as antigen‐presenting cells.J. Leukoc. Biol. 60: 207–213; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.2.207

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractThe resurgence in mycobacterial infection worldwide has led to renewed attention to the pathogenesis ofMycobacteriumspecies. The purpose of this study was to characterize the infection of alveolar macrophages (AMs) by nonopsonizedMycobacterium bovis, and to elucidate the mechanism by which a differential infection of subpopulations of AM may occur. A difference in susceptiblity toMycobacterium bovisinfection of subpopulations of AMs was observed, such that the least dense cells were the least susceptible (21.4 ± 10.7%) and the most dense cells were the most readily infected (61.8 ± 5.6%). The percentage of AMs staining for CD14 receptors showed a similar differential distribution, with fewer of the least dense cells expressing CD14 and a greater percentage of the most dense cells staining for CD14 receptor expression. To investigate the role of CD14 receptors in the infection of AMs, anti‐CD14 antibody was added to the cell cultures. Infection of AM byMycobacterium boviswas blocked by up to 60.2% by anti‐CD14 antibody but not by isotype control antibody. The results of this study suggest thatMycobacterium bovisselectively infects AM subpopulations, specifically those with the greatest expression of CD14, a putative receptor mechanism forMycobacterium bovisinfection of porcine AM.J. Leukoc. Biol. 60: 214–220; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.2.214

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractMice rendered B cell‐deficient either by chronic anti‐μ treatment initiated at birth or by gene knockout (JHD andμ‐MT mice) suppressed acutePlasmodium chabaudiinfections with a time course similar to intact control mice. Moreover, both kinds of B cell‐deficient mice showed a 50‐ to 100‐fold increase in splenic γδ T cell number after suppression of parasitemia compared with uninfected B cell‐deficient controls; the magnitude of this increase resulted in significantly (P<0.05) greater numbers of splenic γδ T cells in the B cell‐deficient mice than in infected B cell‐intact controls (about 10‐fold). In contrast, the number of splenic CD4+αβ T cells was only slightly elevated (<2‐fold) in both kinds of B cell‐deficient mice compared with their intact controls. The number of splenic γδ T cells following suppression ofP. vinckeiparasitemia was approximately ninefold greater in JHDmice than in C57BL/6 controls, whereas similar numbers of splenic CD4+αβ T cells were detected. Maximal numbers of γδ T cells were in cell‐cycle in both JHDand C57BL/6 mice during descendingP. chabaudiparasitemia, but the number of γδ T cells in cell‐cycle was greater in B cell‐deficient mice than in intact controls. Interleukin‐10 (IL‐10), a potent TH1cell‐suppressive molecule, does not appear to down‐regulate the γδ T cell response during malaria in B cell‐intact mice because the magnitude of the γδ T cell response was not significantly greater in IL‐10 knockout mice compared with heterozygote controls. These findings collectively indicate that a markedly enhanced expansion of the γδ T cell population occurs in the absence of B cells, and this expansion occurs predominantly during acute malaria when parasite burdens are similar in B cell‐deficient animals and intact controls.J. Leukoc. Biol. 60: 221–229; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.2.221

出版商:Wiley    

年代:1996

数据来源: WILEY