摘要:

AbstractImmunization of mice with phosphorylcholine (PC)‐bearingStaphylococcus pneumoniaeType 2, strain 36a (R36a) results in both a PC‐specific and a polyclonal increase in splenic plaque‐forming cells. The polyclonal increase was observed in all strains tested, including those bearing an X‐linked immune defect resulting in an undetectable anti‐PC immune response. The magnitude of the polyclonal response is directly related to the amount of bacterial surface PC as detected by enzyme‐linked immunosorbent assay. Congenially athymic (nude) mice mount an anti‐PC plaque‐forming cell response after R36a immunization but fail to produce a significant polyclonal response. From our results it appears that PC on the cell wall of a bacterium acts both as a polyclonal activator and a specific antigen, stimulating each by diffe

ISSN:0014-2980    

DOI:10.1002/eji.1830140702

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractIt has been demonstrated in the preceeding report (Bach, M. A., Beckmann, E. and Levitt, D.,Eur. J. Immunol.1984.14:589) that phosphorylcholine (PC) on the bacteriumStreptococcus pneumoniaeR36a stimulated polyclonal as well as anti‐PC plaque‐forming cells (PFC) in mouse spleenin vivo. In this study, red blood cells from BALB/c mice (MRBC) were either conjugated with PC, 2,4,6‐trinitrophenyl (TNP) or treated with phospholipase A2(PLA2) to expose PC on the cell membrane (determined by hemagglutination with the anti‐PC myeloma HOPC8). When BALB/c mice were immunized i.v. with the conjugated or enzyme‐treated MRBC, a significant polyclonal antibody response ocurred (p<0.05) using PC‐MRBC or PLA2‐treated MRBC, but not with TNP‐MRBC or sham‐treated MRBC. No anti‐PC or anti‐MRBC immunoglobulin‐secreting cells developed after immunization. Repeated immunization with PC‐MRBC resulted in similar levels of protein A PFC after each immunization but no anti‐PC, anti‐MRBC or anti‐PC‐MRBC PFC.Thus, PC on R36a or isologous RBC stimulated increased numbers of splenic plaqueforming cells. In the case of R36a, 10‐25% of these PFC produced antibodies directed towards PC. In contrast, PC‐MRBC or PLA2‐treated MRBC, failed

ISSN:0014-2980    

DOI:10.1002/eji.1830140703

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractMRL/MP‐lpr/lpr(MRL/lpr) mice develop a lupus‐like autoimmune disease and a massive generalized lymphadenopathy associated with proliferation of nonmalignant Thy‐1+Lyt‐1+cells. The mechanism(s) leading to outgrowth of these cells is unknown.We report here that Thy‐1+, Lyt‐1+, Lyt‐2−lymphocytes from spleens of MRL/lpr mice, but not from several strains of normal mice, spontaneously secrete IL3. The presence of IL3 is shown by: (a) the ability of the supernatants from unstimulated spleen cells of MRL/lpr (MRL/lpr SUP) to support growth of IL3 but not IL2 addicted cells and (b) the growth‐promoting activity in MRL/lpr SUP was absorbed with IL3‐dependent cells but not with IL2‐dependent cells. Spontaneous release of IL3 was detected in supernatants from spleen cells of 6‐week‐old MRL/lpr mice and the titers of IL3 activity increased with age.Nylon wool‐enriched cells from spleens of MRL/lpr mice proliferated in response to purified IL3 and IL3 secreted by MRL/lpr T cells, in a manner similar to nylon wool‐passed cells from normal mice. The cells responding to both sources of IL3 were Thy‐1+, Lyt‐1+, Lyt‐2−. Thus, Thy‐1+, Lyt‐1+,2−cells from spleen of MRL/lpr mice spontaneously secrete IL3 and respond normally to this lymphokine.Four Thy‐1+, Lyt‐1+,2−cell lines derived from unstimulated spleen cells of MRL/lpr mice were established in culture with IL3. These IL3‐sensitive T cell lines help syngeneic and H‐2‐compatible normal small “resting” B cells to mature into plasma cells secreting predominantly IgG1, IgG2and IgA.Taken together, these data and previous findings that T cells from MRL/lpr mice have an impaired production of and response to IL2, strongly suggest that abnormal production of IL3 may account for the outgrowth of Thy‐1+, Lyt‐1+,2−cells in the MRL/lpr mouse. Finally, a mechanism linking abnormal produc

ISSN:0014-2980    

DOI:10.1002/eji.1830140704

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractIn a previous study we described an anti‐neutrophil monoclonal antibody, which inhibited human neutrophil chemotaxis and degranulation without any detectable effect on phagocytosis or oxidative metabolism (Cotter, T. G., Spears, P. and Henson, P. M.,J. Immunol.1981.127:1355). This antibody was termed NCD 1. In this study we determined the number of NCD 1‐binding sites per neutrophil. Approximately 25000 NCD 1 IgG‐binding sites per cell were found with an equilibrium dissociation constant (Kd) of 6.5 μM for antibody binding. NCD 1 Fab bound to approximately 39000 sites per cell with a Kd of 16.5 μM. Affinity chromatography columns prepared by coupling NCD 1 to Sepharose 4B beads were used to purify the antigen which bound this antibody. The antigen was a 110‐kDa glycoprotein which was not susceptible to reduction by 2‐mercaptoethanol. The antigen was not internalized following phagocytosis of opsonized sheep erythrocytes by

ISSN:0014-2980    

DOI:10.1002/eji.1830140705

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractThe response to heterologous insulin in H‐2bmice is restricted to the A chain loop determinant(s) of beef insulin. The recognition of this specificity requires the expression of the immune response (Ir) gene epitope Ia. W39 which is absent from the I‐Abmutant B6.C‐H‐2bm12(bm12) mice. This restriction could reflect the inability of H‐2bantigen‐presenting cells (APC) to present other insulin determinants or may reflect “self‐major histocompatibility complex”‐dependent influences on the generation of the T cell repertoire. To assess these possibilities we analyzed the genetic control and fine specificity of the insulin‐specific T cell repertoire of H‐2bmice by fusing the AKR thymoma BW5147 with T cells of C57BL/6 mice which had been immunizedin vivoand challengedin vitrowith beef insulin. The cloned hybridomas that we have produced respond to APC either alone or in conjunction with insulin by the production of interleukin 2. The insulin‐specific hybridomas vary in their fine specificity such that some clones recognize a determinant(s) shared by beef, sheep and pork insulin and the isolated B chain, while other clones recognize a determinant(s) shared by beef and sheep insulin only, likely to involve amino acids 8 and/or 10 of the A chain loop. The presentation of insulin to these hybridomas is restricted by I‐Ab, but not by Ia.W39. This analysis revealed that the insulin‐specific immune potential in H‐2bmice is of greater scope than previously defined and led us to consider, whether insulin nonresponder bm12 mice also possess a latent insulin‐specific immune potential. Our study of the insulin‐specific immune recognition by bm12 mice shows that these nonresponders do possess insulin‐specific T cell clones. Despite the fact that the I‐Aband I‐Abm12gene products differ only by 3 amino acids, insulin‐specific C57BL/6 and bm12 hybridomas are restricted to recognize exogenous antigen only in the context of C57BL/6 and bm12 APC, respectively. Furthermore, upon direct analysis of autoreactive subclones, a similar although not complete, restriction was observed. The implications of these findings for understanding the

ISSN:0014-2980    

DOI:10.1002/eji.1830140706

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractThree subpopulations of human granular lymphocytes from blood and lymphoid tissues were characterized using combinations of the monoclonal antibodies (mAb) HNK‐1 (Leu‐7), Leu‐11 and VEP13. Each subpopulation was confirmed to possess natural killer (NK) cell functional capability, but a different level of cytotoxic efficiency (HNK‐1+Leu‐11−HNK‐1+Leu‐11+

ISSN:0014-2980    

DOI:10.1002/eji.1830140707

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractMonoclonal anti‐idiotype (Id) antibodies with specificities for determinants related to the antigen‐binding sites of 3 BALB/c myeloma proteins, MOPC‐460, HOPC‐8 and J558, were used to study Id expression on murine lymphocytes. The monoclonal antibodies were shown to react only with Id structures associated with immunoglobulin on B cells. None of these 3 Id nor a VHId, detected by a monoclonal antibody made against HOPC‐8 heavy chain, were found on T cells. These Id were detected on splenic B cells in neonatal mice; the frequencies in normal, nude and germ‐free mice were similar: MOPC‐460 Id+: 1.05 ± 1.7/104spleen cells, HOPC‐8 Id+: 1.45 ± 1.2/104and J558: 0.35 ± 0.6/104. Almost all Id+cells bore surface IgM, a few expressed surface IgG. MOPC‐460 Id+IgG+cells were mainly γ2a+or γ2b+, whereas J558 and HOPC

ISSN:0014-2980    

DOI:10.1002/eji.1830140708

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractDuring the course of examining thein vivodevelopment of the cytotoxic T lymphocyte (CTL) response to hapten‐modified self antigens in mice, we have observed that it can be abrogated through prior exposure of the host's regional lymph nodes (LN) to normal syngeneic spleen cells (NSC). Suppression appeared to be antigen nonspecific and was best seen when animals were injected in the footpads with NSC at least 72 h before sensitization for CTL. The ability to prevent the development of the CTL response was restricted primarily to syngeneic splenic T and B cells since syngeneic thymocytes stimulated only partial suppression and syngeneic LN cells, as well as hapten‐coupled syngeneic spleen cells, did not at all. Suppression appeared to be a local phenomenon in that the NSC induced transferrable suppressor T cells to appear in the popliteal LN draining the footpads but not in spleens. In addition, animals splenectomized prior to injections of NSC showed abrogated CTL responses equivalent to sham‐splenectomized animals indicating that the spleen does not contribute to the mechanism of suppression. Finally, when only one footpad was injected with NSC, suppression was seen in the draining popliteal node and not in the contralateral node. Taken together, the evidence suggests that the source of the suppression and the suppressor T cells may be attributed to anin vivosyngeneic mixed lymphocyte reaction occurring between responder cells of the draining LN and injected stimulator spleen

ISSN:0014-2980    

DOI:10.1002/eji.1830140709

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractMonocyte/macrophage‐mediated cytotoxicity requires the generation of activated oxygen radicals, which can be measured by chemiluminescence (CL). To investigate whether natural killer (NK) cell activity required activated oxygen species, both cytotoxicity against K562 target cells and CL were measured in cell populations of human peripheral blood. The following results were obtained: (a) Peripheral blood mononuclear cells (MNC) showed NK activity and a response in CL, which could be induced by viable or paraformaldehyde‐fixed K562 target cells as well as by latex particles, (b) Both T cells and non‐T cells exhibited NK activity, but T cells gave no K562‐ or latex‐induced CL responses, (c) Depletion of phagocytic cells from MNC abolished CL, but only marginally affected NK activity, (d) Reconstitution of phagocyte‐depleted MNC with adherent cells revealed a superadditive enhanced CL response, but had no augmenting effect on NK activity, (e) Phagocyte‐depleted cell populations, enriched for NK activity by density gradient centrifugation, did not respond in K562‐ and latex‐induced CL. (f) MNC, highly enriched for NK activity by cell sorting with a cytofluorograf using the fluorescein isothiocyanate‐labeled monoclonal antibody anti‐Leu‐11a, responded only with reduced CL, whereas the NK activity was enriched up to 45‐fold. From these results it is concluded that NK cell‐mediated cytolysis of K562 target cells and K562‐induced CL are not functionally correlated, but represent properties of two distinct cell populations,

ISSN:0014-2980    

DOI:10.1002/eji.1830140710

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractThe effect of fractionated total lymphoid irradiation (TLI) on the induction of cells blockingin vivoB cell maturation was examined. (BALB/c × C57BL/6)F1mice received 200 rds lymphoid irradiation daily for 8 days. One month after termination of the irradiation splenic T cells of TLI‐treated mice were transferred, together with normal bone marrow cells, to lethally irradiated hosts. In addition, splenic cells or splenic B cells of TLI mice were transferred to irradiated hosts. Two months later, we checked the reconstituted mice for their ability to producein vivoanti‐trinitrophenyl (TNP)‐Ficoll antibodies and their capacity to respondin vitroto dextran sulfate and lipopolysaccharide. In parallel, stained spleen cells were analyzed on the fluorescence‐activated cell sorter using monoclonal anti‐μ, anti‐λ and anti‐B220 surface marker antibodies.The results indicate that splenic T cells originating from TLI‐treated mice cause maturation arrest of normal and TLI‐treated B cells, since normal bone marrow cells injected together with those cells have immature phenotypic and functional features. In addition, neither splenic cells nor splenic B cells of TLI‐treated mice can mature upon transfer to normal irradiated hosts. The B cells are IgM+, IgD−; they respond with a high proliferation rate to dextran sulfate and low proliferation rate to lipopolysaccharide, and poorly

ISSN:0014-2980    

DOI:10.1002/eji.1830140711

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY