摘要:

AbstractThe T3 complex is known to be expressed on the cell surface of mature T cells together with either the α‐β heterodimeric T cell receptor (TCR) or the TCR γ protein. In a number of immature T cell malignancies, however, T3 has been described exclusively in the cytoplasm. We have investigated five such T cell lines with cytoplasmic T3 and could demonstrate by biosynthetic labeling the presence of the α and β chains of the TCR in the cytoplasm of two of them, CEM and Ichikawa. No surface TCR α‐β protein could be detected by staining with the WT31 antibody. These observations, therefore, argue against the concept that expression of the TCR α chain controls the surface expression of the T3/TCR complex. Interestingly, phorbol 12‐myristate 13‐acetate (PMA) induced cell surface expression of T3 protein in these two cell lines only. Moreover, on surface‐iodinated CEM cells no association of T3 and TCR molecules could be demonstrated after treatment with PMA, and expression of TCR α and β chains was limited to the cytoplasm. In Ichikawa cells, however, PMA induced surface expression of a mature T3/TCR complex. Our findings indicate that separate regulatory mechanisms may exist for the surface expression of the T3 proteins and for the assembly of

ISSN:0014-2980    

DOI:10.1002/eji.1830170802

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractFN18, a monoclonal antibody specific for the polymorphic rhesus monkey CD3 antigen on peripheral T cells, has been tested for its immunosuppressive effect in a rhesus monkey skin graft model. Animals were injected i.v. daily with antibody and they received an allogeneic skin graft two or three days after the initial antibody treatment. All animals were carefully monitored regarding levels of the major lymphocyte subsets. In animals in which RhT3 (a CD3‐like antigen) is demonstrable (i.e.FN18+phenotype), all T cells initially disappeared from the circulation. However, T cells without RhT3 on their surface reappeared after several days, indicating that these cells must have been modulated. The survival times of the skin grafts were significantly prolonged in these animals. In monkeys in which RhT3 is not demonstrable (i.e.FN18−phenotype), mainly part of the CD4+lymphocyte subset was depleted. Although less explicit, skin graft survival was significantly prolonged in these animals as well. In both the FN18+and FN18−groups a difference in sensitivity between the CD4+and CD8+cells for the FN18 antibody could be noticed. From the data it appears that FN18 is immunosuppressive and does not have serious side effects. The data are in agreement with information available for the use of OKT3 in clinical immunosuppression. Thus, extrapolation of data from the rhesus monkey model to the clinical situation seems fea

ISSN:0014-2980    

DOI:10.1002/eji.1830170803

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractGranzyme A is a serine esterase initially isolated from cytoplasmic granules of cytolytic T cell lines (Masson, D. et al.,EMBO J.1986.5:1595). Among normal T lymphocytes activated by allogeneic stimulation it is found in both Lyt‐2+and L3T4+subsets in comparable amounts. Here we show that normal alloantigen‐activated T cells secrete the enzyme specifically when mixed with appropriate stimulator cells. Specific enzyme release is dependent on external calcium and removal of calcium blocks further secretion within a few minutes. Both Lyt‐2+and L3T4+cells specifically secrete the enzyme with similar rates, and anti‐L3T4 and anti‐Lyt‐2 antibodies block secretion by the responder cells expressing these markers. Anti‐LFA‐1 antibodies, on the other hand, block secretion b

ISSN:0014-2980    

DOI:10.1002/eji.1830170804

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractThe results presented in this report define a dominant T cell‐recognized public idiotype (SRId) expressed on monoclonal anti‐chicken egg‐white lysozyme (HEL) antibodies produced by hybridomas derived from secondary response lymphocytes. This Id mediates interactions between SRId+B cells and SRId‐recognizing T cells. In the absence of exogenous antigen, irradiated secondary anti‐HEL B hybridoma cells (B‐Hyb) of nonoverlapping specificity can be used to induce a helper T cell population capable of specifically stimulating anin vitroanti‐HEL plaque‐forming cell (PFC) response. Importantly, similar immunizations using carbodiimide‐treated secondary anti‐HEL B‐Hyb cross‐primed for a suppressor T cell population capable of suppressing thisin vitroanti‐HEL PFC response. That is, suppression was seen not only to the response induced by the homologous B‐Hyb but to other B‐Hyb which express anti‐HEL monoclonal antibody of nonoverlapping specificity. This evidence is consistent with the presence of a pre‐existent regulatory Id network involving SRId in antigennaive animals. After immunization with HEL, regulatory cells exert a strong selective pressure which leads to a secondary anti‐HEL B population, of varying fine specifici

ISSN:0014-2980    

DOI:10.1002/eji.1830170805

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractThe thymic hormone, thymopoietin (Tpo), from human (HTpo), bovine (BTpo) and from synthetic (sHTpo) origins bound to the acetylcholine receptor (AChR) solubilized by Triton 1.5% from human muscle. This binding was demonstrated either by inhibition of formation of radiolabeled α bungarotoxin (αBgt)‐AChR complexes measured after precipitation by ammonium sulfate or by a myasthenic serum containing a high concentration of anti‐AChR antibodies, or directly by incubating the human AChR with radiolabeled sHTpo or BTpo. The125I‐labeled αBgt‐AChR complexes were totally inhibited by 10−6M sHTpo or BTpo. The complexes formed by AChR and the radiolabeled Tpo were recognized specifically by sera containing anti‐AChR antibodies from myasthenic patients. The active pentapeptide derivative of Tpo, thymopentin, another thymic hormone, thymulin, as well as bovine insulin did not interfere with the specific binding of αBgt to human AChR. Tpo and anti‐AChR antibodies could participate together in the inhibition of neuromuscular conduction with Tpo modulating the depressive effect of the antibodies on the neuromuscular junction in

ISSN:0014-2980    

DOI:10.1002/eji.1830170806

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractThe synthetic random copolymer of L‐glutamic acid and L‐lysine (GL) is weakly or nonimmunogenic in all inbred strains of mice. Theories proposed to account for nonresponsiveness to GL include a deficient T cell repertoire, failure of antigenpresenting cells to present the antigen and/or the presence of suppressor cells. In this study we examine mechanisms for nonresponsiveness to GL. We demonstrate the existence of GL‐reactive T cells which can be isolated with a relatively high frequency. These clones, which were derived following immunization of H‐2dmice with poly(LGluLLysLTyr), also respond to several GL‐containing polypeptides including the terpolymers of GL with phenylalanine, alanine (GLA) or leucine. Although recognition of GLA by heterogeneous T cell populations usually occurs in association with I‐A determinants, these clones recognize GLA, as well as the other GL‐containing polymers, in association with I‐E determinants. Analysis of the antigen and alloreactivity patterns of these clones indicated that they expressed distinct antigen receptors. These studies imply that the T cell repertoire of “nonresponder” H‐2dmice includes multiple GL‐reactive T cell clones and that the antigen‐presenting cells of these mice are effective in pro

ISSN:0014-2980    

DOI:10.1002/eji.1830170807

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractTo study the long‐term memory response, BALB/c mice were allowed to rest for over a year after a secondary immunization with the hapten 2‐phenyl‐oxazol‐5‐one (phOx). For the tertiary immunization two different protocols were used. In one protocol mice were injected i.v. and 3 days later spleen cells were fused to a nonproducing hybridoma line. PhOx‐specific hybridomas were established and the sequence of the heavy and light chain mRNA was determined. This tertiary response resembled the diversity pattern of the secondary response with a further increase both in somatic mutations and in the average dissociation constant. The high number of somatic mutations demonstrates the persistence of memory B cell clones over a long time period. In the second protocol mice were boosted with an i.p. injection of alumprecipitated antigen phOx and 7 or 14 days later spleen cells were fused. Sequence analysis of heavy and light chain mRNA showed that these tertiary response antibody molecules had surprisingly few somatic mutations, indicating an activation of virgin B cell clones in these hyperimmunized animals. The maturation of these newly stimulated B cell clones seems to follow somewhat similar rules to those found for the primary response. It appears therefore that the two immunization protocols reflect the response of memory and virgin B cells, r

ISSN:0014-2980    

DOI:10.1002/eji.1830170808

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractMice which bear thelprgene spontaneously develop autoimmune syndromes characterized by massive expansion of an unusual T cell subset which is phenotypically Thy‐1+, L3T4−, Lyt‐2−, B220+. The mutant T cells are refractory to stimulation with mitogenic lectins and, by implication, are thought to be solely responsible for the defects in lymphokine production manifested bylprmice. The contribution of the remaining L3T4+T cell subset to the latter derangements has not been previously examined and is the focus of this study. We found that abnormalities in concanavalin A‐induced interleukin 2 and 3 production in the spleens of MRL‐lpr/lprand C57BL/6.lprmice occurred in the presence of limited infiltration with B220+, L3T4−T cells. Mixing experiments indicated that B220+T cells were not suppressive. Furthermore,lprspleen cells enriched for L3T4+cells and depleted of sIg+, B220+and Lyt‐2+cells demonstrated reductions in lymphokine production which were comparable to those seen in unfractionated preparations. Spleen cells from C57BL/6.lprmice, enriched for L3T4+cells, were also markedly impaired in a mixed leukocyte reaction in response to stimulator cells from the class II major histocompatibility complex mutant bm12. The results indicate that the aberrations in lymphokine production and proliferation in the spleen cells oflprmice involve not only B220+T cells but also L3T4+cells and suggest a potential role for the L3T4+subset in the pathogenesis of lupus inl

ISSN:0014-2980    

DOI:10.1002/eji.1830170809

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractTo determine whether the expression of surface IgD (sIgD) influences the extent of the expressed B cell repertoire, the clonal diversity of the B cell population in mice treated chronically with anti‐IgD (delta) antibodies has been compared with the B cell repertoire observed in control animals, using the splenic focus limiting dilution B cell assay. The results show that the phosphorylcholine (PC)‐specific B cell precursor frequency in anti‐delta antibody‐treated mice is increased when compared with that of control mice. Isotype and idiotype (T15) analyses of PC clonal products from anti‐delta antibody‐treated and control mice revealed no distributional differences. Analyses of the 2,4‐dinitrophenyl (DNP)‐ and fluoresein isothiocyanate‐specific B cell repertoires confirmed that the equal or increased precursor frequencies observed in anti‐delta antibody‐treated mice are not specific for the PC antigen. The increased precursor frequency of B cells from anti‐delta antibody‐treated mice was not the result of increased homing of B cells from anti‐delta antibody‐treated mice to recipient spleens, since B cells from control mice homed twice as well to recipient spleens as did B cells from anti‐delta antibody‐treated mice. Other studies demonstrated that (a) on average, antibody‐secreting clones were generated more slowly when B cells from anti‐delta antibody‐treated mice were used as a source of precursors than B cells of control mice and (b) both sIg−spleen cells and sIg+spleen cells from anti‐delta antibody‐treated mice generated a higher frequency of specific antibody‐secreting clones than did the corresponding populations from control mice. These observations suggest that a population of sIgM+sIgD−B cells exists that resembles sIgD+B cells rather than neonatal orxidB cells in its ability to generate responses to PC and suggests that the sIgM+sIgD−B cells from anti‐delta antibody‐treated mice are more responsive than are sIgM+IgD+B cells, regardless of antigenic specificity, to the stimuli provided in the splenic focus system. Finally, this study suggests that the expression of sIgD does not

ISSN:0014-2980    

DOI:10.1002/eji.1830170810

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractAt least two factors with the capacity to induce IgM synthesis in human B cells were found to be present in the 15–20‐kDa fraction of the supernatant of mononuclear cells activated with concanavalin A (Con A) and phorbol ester. Previously, it has been shown (Sauerwein, R. W. et al.,Eur. J. Immunol.1985.15:611) that interleukin 2 (IL 2) in this material is able to induce T cell‐dependent IgM secretion in normal B cells. Evidence was obtained for the presence of another factor distinct from IL 2 that could replace T cells in the induction of B cell differentiation. We have analyzed this factor with the use of a neoplastic B cell population of prolymphocytic origin that was functionally nonresponsive to IL 2. T cell‐replacing factor (TRF)‐like activity and IL 2 could be separated by ion‐exchange chromatography, although a small amount of IL 2 was recovered in the TRF fractions. This small amount of IL 2 was found to be crucial for the observed TRF activity. Moreover, a substantial amount of monomeric Con A was detected in the TRF preparation. Our studies show that Con A in the presence of IL 2 can act as a potent inducer of helper function in lower numbers of T cells for normal and neoplastic B cells. Functional assays for T cell contamination in B cell suspensions are therefore of limited value because they are determined by the efficiency of the stimulating signal. Particularly in those B cell factor preparations, obtained from mitogen‐activated T cells with an obligatory or unidentified role of IL 2, the possible effect of a contaminating mitogen must

ISSN:0014-2980    

DOI:10.1002/eji.1830170811

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY