摘要:

AbstractThe effects of interleukin 2 (IL2) on the proliferation and differentiation of B cells were analyzed separately using cells from two patients suffering from B‐type chronic lymphocytic leukemia. The monoclonal B cells from these patients exhibited an opposite pattern of responsiveness uponin vitroculture with IL2 in the absence of other stimuli. In the first patient, IL2 alone was able to induce DNA synthesis and no Ig production. In the second patient, although no DNA synthesis was detected, B lymphocytes synthesized IgM upon stimulation with IL 2 alone. Analysis of mRNA levels was performed on the cells of this latter patient after culture without or with IL2. In the presence of IL 2 we observed a strong enhancement of Cμgene expression associated with an increase of the ratio between the secreted form and the membrane‐bound form of μ mRNA. In contrast IL2 induced only a marginal enhancement of J chain mRNA. Thus, terminal B cell differentiation of selected monoclonal B cells can be obtained in the absence of DNA synthesis and IL2 alone can mediate this process. Moreover, IL2 can act at selective steps of the molecular events associated with IgM production. These results document the multiple effects of a given IL on the events leading to antibody production and strongly suggest that they can be conditioned by the maturation stage of a given responding

ISSN:0014-2980    

DOI:10.1002/eji.1830181002

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractBurkitt's lymphoma cell lines Ly91, Ly47 and JBL2 contained intracytoplasmic μ chains without light chains and variably expressed membrane μ chains. All three cell lines produced similarly truncated heavy chains with an apparent molecular mass of 64 kDa instead of the normal 74 kDa. Both the intracellular and secreted forms of the μ chains were similarly truncated. The membrane and the secreted forms of μ mRNAs were shorter than normal. The cDNAs contained a leader sequence, followed by about one third of a variable region (VH), then by the constant region (Cμ). Interruption of the variable region took place near the end of the framework region 1 (FR1) in Ly47 and JBL2, and within the complementarity determining region 1 (CDR1) in Ly 91. In the three lines, the joining between VHand Cμmaintained the normal open reading frame throughout the variable and constant re

ISSN:0014-2980    

DOI:10.1002/eji.1830181003

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractA new heterodimeric structure, Tp135‐145, which can mediate interleukin 2 (IL2) production and Ca2+mobilization by Jurkat cells is described. This structure was identified by a monoclonal antibody, MX24, on the surface of either T3/TcR+or T3/TcR−human T cell lines as well as on B cell lines.Biochemical studies showed that antibody MX24 precipitated two polypeptide chains of 135 and 145 kDa, respectively, in lysates from125I‐labeled T cells. After reduction the 135‐kDa polypeptide chain shifted to 140 kDa, whereas the molecular mass of the other polypeptide remained unchanged. The apparent molecular masses of the desialylated polypeptides differed by 5 kDa. No common peptide fragments between the two polypeptide chains were found after limited proteolysis byStaphylococcus aureusV8 protease.The expression of Tp135‐145 was independent of the expression of the T3/TcR molecular complex. Incubation of Jurkat cells with anti‐TcR or anti‐T3 monoclonal antibody induced complete modulation only of the T3/TcR complex but not of Tp135‐145. Conversely complete modulation of Tp135‐145 was observed after incubation of these cells with MX24 antibody. Functional studies showed that anti‐Tp135‐145 antibody MX24 induced high levels of IL2 production in Jurkat cells. In addition, incubation of these cells with MX24 resulted in Ca2+mobilization from internal stores. In peripheral blood, Tp135‐145 was found to be expressed by 39%‐76% of resting T cells in individual donors. Two‐color flow microfluorimetry showed that the Tp135‐145′ cells were equally distributed on the CD4+and CD8+subsets.Incubation of peripheral blood T cells with antibody MX24 resulted in IL 2 production and cell proliferation. Taken together these results suggest that Tp135‐145 is a novel surface molecule involved in antigen‐indep

ISSN:0014-2980    

DOI:10.1002/eji.1830181004

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractThe Obese strain (OS) of chickens, which is afflicted with Hashimoto‐like spontaneous autoimmune thyroiditis (SAT), displays elevated T cell proliferation, interleukin (IL) 2 production and IL2 receptor expression upon mitogen stimulation, and defects in the neuroendocrine control of the immune system including elevated corticos‐teroid‐binding globulin (CBG) and a deficient increase of serum corticosterone (CN) upon cytokine injection. Recently this strain has further been shown to harbor retrovirus‐related sequences (endogenous virus no. 22,ev22) absent in healthy control strains. To determine the number of genes responsible for SAT‐associated immunodysregulation and to unravel possible ev22 associations, we analyzed the above immune and endocrine parameters in F1hbrids and backcrosses of the autoimmune OSB15B15with healthy inbred CBB12B12chickens.OS‐like T cell hyperproliferation and IL2 hypersecretion in response to both con‐canavalin A and phytohemagglutinin were transmitted as autosomal dominant traits and co‐segregated in backcross animals.In vivohyporesponse of the OS to the cor‐ticosterone‐inducing effect of cytokine preparations was inherited dominantly and the elevated CBG serum levels recessively. None of these traits appeared to be major histocompatibility complex (MHC) linked. However, while T cell abnormalities and elevated CBG serum levels were not associated with the autosomalev22locus,in vivohyporesponsiveness to glucocortocoid‐inducing cytokines co‐segregated with this OS‐specific provirus.These results add to the concept of SAT as a polyetiological and plurigenetic disease and do not support our previous hypothesis that T cell hyperreactivity and immunoen‐docrine dysfunction mi

ISSN:0014-2980    

DOI:10.1002/eji.1830181005

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractLysis of human lymphocytes by autologous complement had been studied using a range of monoclonal antibodies against different antigens. Antigen specificity (and not antibody isotype) was the most important factor which influenced cell lysis and this could not be accounted for merely by differences in surface density between antigens. Three antigens with comparable surface density were studied in detail: CAMPATH‐1 (lytic), major histocompatibility complex class I (lytic) and leukocyte common antigen (poorly lytic). Clq binding was roughly proportional to antibody binding and dependent on antibody isotype. However, the lytic antibodies were much better able to bind and activate whole C1 than the poorly lytic ones. This result would not have been predicted from traditional concepts of complement activation but can be interpreted in the light of models for C1 activation which involve Fc‐Fc interactions, Fc‐Clr2s2interactions and a critical Clq stein‐arm angle for C1 binding and act

ISSN:0014-2980    

DOI:10.1002/eji.1830181006

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractThe structure of the murine interleukin 2 receptor (IL2R), on a cytotoxic (CTLL) and a helper (HT2) cell line, has been studied by a combination of chemical cross‐linking with125I‐labeled IL2 and immunoprecipitation with an anti‐receptor monoclonal antibody (7D4). In CTLL cells both methods detected the major 57‐kDa IL2‐binding protein and in addition the cross‐linking studies revealed the presence of a 70–75‐kDa protein associated with the high‐affinity receptor. In the HT2 cell line, however, immunoprecipitation studies revealed three additional proteins of 18, 22 and 37 kDa to the expected 50‐kDa receptor protein. Again cross‐linking studies demonstrated the presence of a 70–75‐kDa protein, which was not immunoprecipitable with the 7D4 antibody. The low molecular polypeptides in HT2 cell were associated with the low‐affinity receptor and represented most likely breakdown products of the 50‐kDa protein. Whereas the 18‐ and 22‐kDa proteins were involved in ligand binding, the 37‐kDa fragment carried the epitope recognized by the 7D4 antibody. Comparative studies with two IL2R antibodies, PC61 and 7D4, revealed that only PC61 inhibited the formation of the IL2 α/β chain complex, although both antibodies reportedly prevent the biological response to IL2. It is speculated that the 37‐kDa fragment, which reacts with the 7D4 antibody, might be involved in IL2 signal transduction. Finally there was no evidence for the existence of a high molecular weight component of the IL2R, previously described as γ chain.In summary, the two‐chain structure of the IL2R has been confirmed for both murine cell lines with some heterogeneity of the α chain. The possibility was raised that a 37‐kDa fragment of the

ISSN:0014-2980    

DOI:10.1002/eji.1830181007

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractA cDNA clone encoding the variable region of the heavy chain of a BALB/c anti‐bromelinized mouse red blood cell (BrMRBC) monoclonal antibody has been characterized. The nucleic acid sequence indicates that the variable region of the heavy chain is likely encoded by variable‐VCP12, diversity‐DSP 2 (5, 7 or 8) and joining‐JH1 germ‐line genes. An identical combination of V genes was observed for six other CBA/J and NZB anti‐BrMRBC hybridomas. The BALB/c VCP12 nucleotide sequence is less than 80% homologous to members of the 10 known VHfamilies. Moreover, the genomic restriction fragments detected under moderate stringency conditions with the radiolabeled cDNA probe did not correspond to those obtained with probes of the most homologous VHfamilies (7183 and X24).The results indicate that the VCP12 gene defines a new VHfamily which we propose to designate vH11. The observation of 1, 2 or 3 enomic restriction fragments at the most, with mice bearing the Igh‐Vd or J, Igh‐Va or bF or Igh‐Vchaplotypes, suggests the existence of a few VC

ISSN:0014-2980    

DOI:10.1002/eji.1830181008

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to evaluate the effect of recombinant granulocyte‐macrophage colony‐stimulating factor (rGM‐CSF) on BALB/c mice infected s.c. with the intracellular pathogenLeishmania major.Daily i.p. application of 1 μ rGM‐CSF for 21 days following the infection led to an aggravated course of the disease in most animals. In no case was a therapeutic effect observed.In vitroanalysis revealed that the parasite burden was approx. 2‐ to 7‐fold higher in the infected lesions, in the lymph nodes draining the infection and in the spleens of rGM‐CSF‐treated animals than in tissues from nontreated mice.L. major‐infected macrophages obtained from chronically infected mice proliferated in the presence of rGM‐CSFin vitrowithout gaining antiparasitic effector function. However, antiparasitic effector function increased and macrophage growth was inhibited in the presence of recombinant interferon‐γ (IFN‐γ). These data indicate that rGM‐CSF‐induced macrophage proliferation alone is not sufficient to overcome infections with intracellular pathogens likeL. major, since simultaneous activation of ma

ISSN:0014-2980    

DOI:10.1002/eji.1830181009

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractIn this study we have investigated the specificity of bioassays in which interleukin (IL)1 and/or IL6 are active. The thymocyte assay cannot be used to discriminate between IL1 and IL6; both monokines are active in this assay. Moreover the detection limit for both IL1 and IL6 is around 100 pg/ml. IL6 activity can be measured with a murine hybridoma cell line (B9). The detection limit for human as well as murine IL6 is about 0.5 pg/ml. The assay is specific for IL 6 and is not influenced by a variety of other cytokines except for murine IL4 which shows some activity in this assay. IL1 can be measured specifically with D10 cells. The detection limit for IL1α and IL1β is around 1 pg/ml whereas IL6 is not active in this assay at all. Upon stimulation by IL1 and/or IL2 D10 cells produce IL6. However, this IL6 does not seem to be involved in the proliferation of these cell

ISSN:0014-2980    

DOI:10.1002/eji.1830181010

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractThe human CD2 antigen is a T lymphocyte cell surface glycoprotein that has been implicated in both T lymphocyte adhesion and activation. The requirement for a T lymphocyte‐specific factor(s) in the mechanism of signal transduction initiated via the CD2 antigen has been explored using murine L cells transfectants that stably express the human CD2 antigen at the cell surface. Such transfectants express the three CD2 epitopes previously defined on human T lymphocytes. However, combinations of CD2 monoclonal antibodies, that stimulated an increase in the cytoplasmic calcium concentration of the human T cell line Jurkat, failed to induce a similar signal in the transfectants. These results indicate that the transfected CD2 antigen cannot alone transduce intracellular signals in response to stimulatory combinations of CD2 monoclonal antibodies, and suggest that the functional CD2 antigen expressed on human T lymphocytes requires the association of another, as yet undefined factor(s

ISSN:0014-2980    

DOI:10.1002/eji.1830181011

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY