摘要:

SummaryAll vertebrates and invertebrates manifest self/non‐self recognition. Any attempt to answer the question of adaptive significance of recognition must take into account the universality of receptor‐mediated responses. These may lake two forms: (1) rearranging, clonally distributed antigen‐specific receptors that distinguish in the broadest sense between self and non‐self, and non‐self A from non‐self B, latecomers on the evolutionary scene; (2) pattern recognition receptors, the earliest to evolve and still around, necessitating the requirement for induced second signals in T‐ and B‐cell activation. Either strategy need not force upon invertebrates the organization, structure and adaptive functions of vertebrate immune systems. Thus, we can freely delve into the unique aspects of the primitive immune mechanisms of invertebrates. In contrast, using the opposite strategy which is still problematic, i.e. linking invertebrate and vertebrate defence, seems to give us an approach to universality that might eventually reveal hom

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02857.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Seventy‐five per cent of sera from HIV‐I‐infected individuals bind to the human B‐lymphoma cells bearing the major histocompatibility class II molecule in enzyme‐linked immunosorbent assay (ELISA). The binding is caused by the antibodies against the class II molecule present in the serum samples which prevent the interaction of murine anti‐HLA.DR monoclonal antibody with B lymphoma in FACS analysis. The three highly conserved amino acid sequences in α‐ and β‐ chains of the class II molecule and three homologous fragments in HIV‐1 gp120 and gp41 were identified by computer search and synthesized. Using these peptides it was demonstrated that 28–48% of HIV‐positive sera contain antibodies that cross‐react with the peptide of HIV‐I origin and with the peptide from th

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02858.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Subjects with Down's syndrome (DS), or trisomy 21, have an increased susceptibility to infections, malignant diseases and autoimmune phenomena. Various arms of the immune system are severely impaired in trisomie patients. We found that the proportion of blood lymphocytes bearing the γ/δ T‐cell receptor (TCR) was significantly higher in adults with trisomy 21 than in age‐ and sex‐matched healthy controls. Interestingly, the increase was mainly due to an over‐expansion of cells which bear non‐covalently bound γ/δ chains on their surface. This contrasts with the normal blood picture, where the great majority of γ/δ T cells express the disulphide‐linked form of the TCR. The fact that trisomie γ/δ T cells are both numerically and phenotypically unbalanced provides further evidence that immunological abnormalities are inte

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02859.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Tumour necrosis factor α (TNF) is a multipotent cytokine which affects many biological properties of both normal and neoplastic cells. Here we show that treatment with TNF reduces B16‐A melanoma cell susceptibility to normal and in vivo‐ and in vitro‐activated NK cell‐mediated killing. This resistance is associated with an enhancement of B16‐A metastatic potential in normal syngeneic mice, but not in anti‐asialo GM1‐treated animals, further supporting the NK dependence of TNF‐induced enhancement of metastatic ability. A significant increase of MHC class I expression on B16‐A murine melanoma cells is observed after TNF treatment. In all these effects TNF interacts positively with interferon γ (IFN γ). Taken together, these results indicate that TNF treatment negatively affects the susceptibility of B16‐A murine melanoma to NK effectors in vivo and in vitro. This decreased susceptibility may be related, at least in part, to enhanced expression of MHC class I an

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02860.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

‘Naturally’ activated (NA) or resting T lymphocytes obtained from the spleen of normal BALB/c mice were compared in their capacity to mount a syngeneic mixed lymphocyte reaction (SMLR). Both T‐cell subsets were able to proliferate and secrete IL‐3/GM‐CSF in SMLR cultures. IL‐2 was present in ‘resting’ T‐cell SMLR supernatants, and barely detectable in NA T‐cell SMLR supernatants. Both NA and ‘resting’ T‐cell SMLRs were inhibited with anti‐class II, anti‐CD4, or anti‐IL‐2R MoAbs. NA T cells exhibited a background proliferate and secretory activity in the absence of syngeneic accessory cells. This autonomous activity was susceptible to anti‐CD4, but poorly inhibited with anti‐class II MoAbs. Both NA and ‘resting’ T lymphocytes displayed strong responsiveness to allogeneic stimuli. The analysis of the relative frequency of proliferating cells in the SMLR (BALB/c), or allo‐MLR (B10, B10.A, B10.D2) from NA or ‘resting’ T cells indicated an enrichment for syngeneic reactivity among NA T lymphocytes.The meaning of these results for

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02861.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Experiments were performed to analyse the natural killer cell (NK)‐like cytotoxicity frequently expressed by human antigen‐specific cytolytic T lymphocytes (CTL). To this end, several monoclonal antibodies (MoAbs) previously shown to identify a novel function‐associated molecule (FAM) involved in human NK function were utilized. Flow cytometry revealed that these MoAbs reacted with the majority of human NK, but only with a subpopulation of CTL isolated from primary mixed lymphocyte cultures. Preincubation of CTL with the MoAbs inhibited the NK‐like lysis of K562 targets. Experiments with anti‐CD3 MoAb demonstrated that neither the NK‐like cytotoxicity of CTL nor the lytic activity of NK were mediated by the CD3 complex. Expression of the novel FAM was found to develop in T‐cell cultures at the time that NK‐like cytotoxicity was observed. Repeated in vitro antigenic stimulation of CTL was shown to result in loss of NK‐like cytotoxicity, as well as loss of the FAM on the CTL surface. Thus, NK‐like cytotoxicity displayed by antigen‐specific CTL appears to be mediated by a novel FAM that is identical to that

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02862.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Peripheral blood lymphocytes activated with either the calcium ionophore A23187 or the combination of anti‐CD2 monoclonal antibodies. 9.6+VIT13, undergo blast formation and proliferation but do not develop cytolytic activity. These proliferating blasts, referred lo as pre‐effector blasts because they do not yet express cytolytic function, respond to stimulation with interleukin‐2 (IL‐2) by further proliferation and development of cytolytic activity, i.e. they become effector cells. Pre‐effector blasts activated with 9.6 +VIT13, but not A23187‐activated pre‐effector blasts, also respond to stimulation with interferon‐gamma (H N‐γ) by becoming cytolytic effector cells. This report examines gene expression (by Northern blot analysis) in pre‐effector blasts and during the transition from the pre‐effector to the effector stage. The data presented here provide further support for the concept that A23187 activation drives T cells to become dividing blasts that are appropriately referred to as ‘pre‐affector’ cells in that these blasts do not express transcripts for granzyme A or perforin mRNA but are driven by IL‐2 to do so in parallel with the acquisition of cytotoxic function. Cells are apparently driven by 9.6 +V IT 13 to a later stage of functional maturation than by A23187 activation; 9.6 +VIT13‐activated pre‐effector blasts express mRNA for both granzyme A and perforin, even though these blasts do not express cytolytic activity. Activation via A23187 results in lower expression of the proto‐oncogene c‐myb relative to that found in ei

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02863.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Injections of murine gamma interferon (IFN‐γ) into BALB/c nude mice induced Ia expression by keratinocytes The aim of the present study was to use this murine model to determine the effect of ultraviolet radiation (UV) or cyclosporine A (CyA) on Ia expression by keratinocytes. Two sets of experiments were performed. In the first, mice were injected intraperitoneally with IFN‐γ for 6 days. The mice were divided into three groups. One group, with one ear protected by electrical tape, was exposed to UVB radiation for 15 days starting 4 days before the injection. The second group received subcutaneous injections of CyA simultaneously with the IFN‐γ and during the 10 days following the IFN‐γ injection. The third group received only IFN‐γ injections. Fifteen days alter the IFN‐γ injection all mice were killed and evaluations of la positive cells were performed. In the second set of experiments the nude mice were treated with CyA or UVB only 10 days after the last IFN‐γ injections. In both experiments UVB inhibited and down‐regulated la expression by keratinocytes. This effect on keratinocytes was not observed in the protected ears. Thus it appears that the effect of UVB on keratinocytes is local and not systemic. CyA failed to inhibit or down‐regulate Ia expression. This study may shed some light on understanding the mechanism effect of UV radiation in a

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02864.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Activation of T cells is a complex process which we have hypothesized involves a series of functional intermediates possessing some, but not all, of the characteristics of fully functional effector cells. We have identified two such functional intermediates, the poised T cell (po Tc) and the pre‐effector T cell (pe Tc). poTc do not proliferate or mediate cytolytic activity but are responsive to help in the form of interleukin 2 (IL‐2); peTc are proliferating cells which arc not cytolytic. Here the role of T‐cell receptor/CD3 complex cross‐linking in generating these functional intermediates is examined and it is shown that cells can be driven to different stages of functional maturation depending upon the sequence of antibody binding to CD3 and cross‐linking. Highly purified T cells can be activated to poTc stage if they are first labelled with the anti‐CD3 monoclonal antibody OKT3 and then cross‐linked with goat anti‐mouse IgG‐coated beads. If the OKT3 antibody is first bound to the IgG‐coaled beads and then added to highly purified T cells, peTc are generated. In both cases the intermediates can be driven to become fully functional effector cells by the addition of IL‐2. Finally, by removing the OKT3‐bound beads during the activation process, were are able to show that po Tc and pe Tc are sequential intermediates along the sam

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02865.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The role of ELAM‐1 in the adhesion of monocytes to HUVEC, activated for 4 h with TNF, was studied using MoAb ENA2 directed against ELAM‐1. In a standard adhesion assay at 37 C, F(ab')2fragments of f ENA2 did not, or weakly inhibited adhesion. When metabolic activity of the monocytes was reduced by (i)fixing the monocytes, (ii) performing the adhesion assay at 4°C, and (iii) combining the forementioned conditions, the adhesion of the monocytes was strongly blocked by ENA2 and less effective or not by MoAb IB4 anti‐CD18. The pattern of adhesion of monocytes to HUVEC, activated with TNF assessed at 4°C. paralleled ELAM‐1 expression on the endothelial cells. Maximal inhibitory effect of ENA2 on adhesion was shown 5 h after activation of HUVEC, at which ELAM‐1 expression was also maximal. Adhesion assessed at 37°C remained enhanced for at least 24 h, whereas the inhibitory effect of ENA2 followed ELAM‐1 expression. Specific involvement of ELAM‐1 was also confirmed using ELAM‐1 transfected COS cells. These results indicated that monocytes express a counter structure for ELAM‐1 and that this counter structure is

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02866.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY