摘要:

We examined the characterization of the antiviral T lymphocytes elicited by immunization with a novel liposome vaccine (MDP‐virosome) constructed with synthetic muramyldipeptide:[6‐0‐(2‐tetradecylhexadecanoyl)‐N‐acetylmuramyl‐L‐alanyl‐D‐isoglutamine], cholesterol, influenza virus haemagglutinin and neuraminidase. The haemagglutinin glycoprotein first appeared to induce a significant subtypespecific cytotoxic activity through its arrangement on the inner and outer surfaces of the MDP‐virosome. Splenocytes of BALB/c mice immunized with the virosome vaccine containing H3 haemagglutinin and N2 neuraminidase from human Hong Kong virus markedly lysed H3N2 virusinfected target cells, but not those infected with virus possessing a different subtype such as H1N1 surface antigens. Exposure of these splenic lymphocytes to virus antigenin vitrofurther enhanced their cytotoxic activity. The cytotoxic lymphocytes generated by the MDP‐virosome vaccine expressed Thy 1 and CD4 antigens on their cell surface, and these activities were restricted by class II histocompatibility gene products. The marked reduction of pulmonary virus litres in infected mice caused by transferred immune spleen cells suggested that the MDP‐virosome vaccination is able to protect against influenza virus infection through enhanced

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03526.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Distribution of different subpopulations of T cells in the dermal lesions, lymph nodes and peripheral blood of post kala‐azar dermal leishmaniasis (PKADL) patients was studied by using appropriate phenotypic markers for CD2+, CD4+and CD8+cells. Histopathological studies of skin lesions showed marginal to massive infiltration of mononuclear cells depending upon the duration of illness and type of lesions. Thus, while the hypopigmented patches were represented by small focal collections of lymphocytes with scanty parasites in the dermis, these were replaced at the nodular stage with massive granulomas consisting of lymphocytes, plasma cells and histiocytes with numerous amastigotes. The involvement of CD4+and CD8+cell types in these lesions also showed a gradual change from the appearance of a few cells of both the phenotypes in early hypopigmented type to massive accumulation of cells, primarily of CD8+phenotype, in the granuloma of nodular type. However, the observed preponderance of CD8+cells at the lesion site of chronic PKADL patients is in contrast to their peripheral blood CD4+/CD8+cell ratio (1.9:1) which remained within the normal limits. Similar studies of lymph nodes from PKADL patients with lymphadenopathy revealed infiltration of the cortical areas by T cells which were more of CD8+than CD4+phenotypes. All these results document the involvement of CD8+cells in leishmanoid lesions. Thus, it is likely that these cells, in association with appropriate subpopulations of CD4+cells, play a profound role in the evolution of dermal pathology in PKAD

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03527.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Enhancement of virus infectivity after sCD4 treatment has been documented for SIVagm and HIV‐2. It has been suggested that a similar phenomenon may play a role in HIV‐1 infection. In the present study we have analysed biological activities of virus neutralizing polyclonal and monoclonal human antibodies and of sCD4, towards HIV‐1 chimeras with envelope proteins derived from one donor, which display different biological phenotypes. The antibodies, which recognize the V3 and/or the CD4 binding domains of the glycoproteins of these viruses and also sCD4 showed different levels of virus neutralizing activity toward the syncytium inducing HIV‐1 strains. In contrast, they all dramatically enhanced the infectivity of an HIV‐1 chimera with an envelope glycoprotein displaying the non‐syncytium‐inducing phenotype. Given the relatively conserved nature of non‐syncytium‐inducing HIV‐1 surface glycoproteins early after infection, these data suggest a major role for antibody mediated enhancement of virus infectivity in the early pathogenesis

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03528.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Resting T cells can be activated by selected pairs of anti‐CD2 MoAb. Activation is dependent on the presence of accessory cells, which can be replaced by either anti‐CD28, or by the combination of IL‐1β and IL‐6. The present study was undertaken to investigate accessory signalling by B7‐1, the natural ligandof CD28, in this pathway of T cell activation. 3T6 mouse fibrobiasts were transfected with human B7‐1 and used as accessory cells in cultures of purified resting human T cells. In the presence of a stimulating pair of anti‐CD2 MoAb, T cell proliferation, production of cytokines (IL‐2, IL‐4, IL‐10, GM‐CSF, IFN‐α and TNF‐α), and generation of cytotoxic T lymphocytes were all supported by B7‐l(+) 3T6 cells but not by control 3T6 cells. Blocking studies with anti‐IL‐2 + anti‐IL‐2R MoAb revealed both IL‐2‐dependent and IL‐2‐independent CTL generation after B7‐1 ‐mediated costimulation. Moreover, a partial or complete resistance to inhibition with CsA was observed for IL‐2 production and CTL generation respectively in the presence of the costimulatory signal derived from B7‐1 ‐ CD28 interaction. Anti‐CD2 MoAb with B7‐1 costimulation could directly induce proliferation, IL‐2 production and generation of CTL activity in highly purified CD8+T cells without the heip of CD4+T cells. We conclude that CD28 ligation with the natural ligand B7‐1 provides a str

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03529.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

To examine the complex role of cytokines in the pathogenesis of actively induced murine EAE we measured the levels of a number of cytokines (IL‐6, IFN7 and TNF) in the spinal cord and CSF of mice with active experimental autoimmune encephalomyelitis (EAE) and found them all to be elevated. We next treated mice with antibodies to these three cytokines, which were over expressed in the CNS, to determine if they would alter disease and found the following: anti‐IL‐6 had no significant effect on disease, anti‐IFNγ exacerbated disease, and anti‐TNF either enhanced, had no effect or inhibited EAE depending on the antibody used. We then treated mice with exogenous cytokines, delivered using a recombinant vaccinia virus system, and found that the IL‐6 and TNF virus constructs inhibited EAE whereas the IFN1β construct had no effect on disease. Other cytokine recombinant viruses were also tested and it was found that the IL‐1β, IL‐2 and IL‐10 viruses inhibited EAE while an IL‐4 virus either had no effect or enhanced disease. We do not know the mechanism of action of the various cytokines in this system, but irrespective of the mechanism(s), this work clearly demonstrates that delivery of select cytokines using recombinant virus‐cytokine constructs can provide a powerful means of downregulating experimental organ‐s

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03530.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

To test if freshly isolated tumour‐infiltrating lymphocytes (TIL) can induce apoptosis in a target cell, we have combined two previously described methods. Because TIL predominantly are T‐lymphocytes. we have applied a redirected approach. When the target cells that express anti‐human‐CD3 monoclonal antibodies in their membranes bind to the T cell receptor‐associated CD3‐complex, signals are generated, which activate T cell effector mechanisms. This approach circumvents problems with MHC‐restriction and allows for functional testing of all T cells, irrespective of their clonal specificity.In order to assay for induction of DNA fragmentation, we have labelled the target cell nuclei with [3H]thymidine. Upon harvesting fragmented DNA are washed away. Electrophoretic analysis of the fragmented DNA demonstrated the characteristic ‘ladder’ pattern, consistent with apoptosis.This rapid and simple assay monitors the capacity of different T cells to induce apoptosis in the target cell. It depends on intercellular interactions and clearly discriminates between different T cell subsets. With this assay we demonstrate the functional integrity of the cytotoxic effector arm of fre

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03531.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

In African trypanosomiasis the occurrence of antibodies to interferon‐γ (IFN‐γ) was studied in both humans and experimental rats. Sera from patients infected withTrypanosoma brucei gambienseshowed increased levels of antibodies to IFN‐γ as compared with controls from the same regions in Africa. In Sprague‐Dawley rats infected withTrypanosoma brucei bruceian early appearance of IFN‐γ‐producing spleen cells was observed, followed by an increase in levels of antibodies against IFN‐γ in the sera. Previously, IFN‐γ has been found to play a crucial role in trypanosome infections in rats by promoting proliferation ofTrypanosoma brucei brucei. The appearance of antibodies to IFN‐γ in humans, as in rats, indicates that this cytokine is produced also in the human infection. Its parasitic growthstimulating and pathophysiological effects on the organism may be r

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03532.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

It has been shown previously that A60, an antigen complex ofMycobacterium hovisBCG, triggers humoral and cellular immune reactionsin vivoand lymphocyte‐dependent macrophage activationin vitro.In the present work, the ability of A60 to prevent murine tumour development, in conjunction or not with irradiated isologous cancer cells, was explored with Taper liver tumour (TLT), a mammar‐y‐derived neoplasm (EMT6), and Lewis lung carcinoma (3LL). Repeated injections of A60 prior to challenge reduced the incidence of EMT6 and 3LL solid tumours and increased life span. This effect was enhanced by simultaneous administration of 7‐irradiated cancer cells (80–100% suppression of EMT6 and 3LL tumour growth). In mice developing or rejecting tumours, the status of humoral and cellular immunity was evaluated by A60‐based immunoassays. Tumor development was accompanied by a rapid decrease of both anti‐A60 IgG titre in blood and A60‐triggered delayed hypersensitivity reactions. Moreover, A60‐induced T lymphocyte proliferation and macrophage‐dependent autologous cancer cell cytolysis declined progressively during the course of tumour growth. In case of successful immuno‐therapy, a pattern similar to that of unchallenged controls was observed. Our results suggest that A60 promotes cancer rejection via tumour infiltration by lymphocytes and macrophages activated by A60‐specific T lymphocytes. An increased processing of tumour‐specific antigens and activation of tumour‐infiltrating lymphocytes is induced by administration of irradiated cancer ce

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03533.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

T cell precursors in the chick embryo have been localized into the intraembryonic mesenchyme (IEM) and into the para‐aortic region before the first wave of the thymic colonization on embryonic day (ED) 6, 5–8. The cell surface markers of avian prethymic stem cells are not known. It is also not known whether these precursor cells are already committed to the T cell lineage before their thymic colonization.In 7‐day‐old chick embryos Ov+cells were found in the para‐aortic region. Also the endothelial cells of the embryonic dorsal aorta were positively stained. Ov antigen might represent a very primitive marker for precursor cells having the potentiality to differentiate both to haemopoietic and endothelial cells. Scattered CD45+cells were observed in the same para‐aortic area as in many haemopoietic areas in the loose embryonic mesenchymal tissues. CD8α (MoAb 3–298) expressing haemopoielic cells were detected before thymic colonization on ED6. In flow cytometric analysis of IEM precursors Ov, CD45 and CD8α expressing cells seemed to form distinct subsets suggesting heterogeneity of these hae

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03534.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Growth requirements of human natural killer cells in IL‐2‐supplemented cultures were studied, NK cell proliferation was monitored by the MAC (morphology antibody chromosomes) technique and subset specific cell cycle analysis, which both enable direct determination of cell growth in specific lymphocyte subsets among heterogeneous lymphocyte populations. Our results show that even in the presence of saturating concentrations of IL‐2, the proliferative capacity of purified CD16+cells is quite low, but can be stimulated in a dose dependent manner by CD4+cells. CD4+cells could partially be replaced by IL‐4 but not by various other commercially available cytokines. These results provide further evidence of the requirement of accessory stimuli in NK cell proliferation, and support the interpretation that NK cells have a direct regulatory role in specific T cell re

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03535.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY