摘要:

AbstractMouse hybridomas generated by fusion between a lactate dehydrogenase‐B (LDH‐B)‐specific B10.A(2R) T suppressor (Ts) cell line and the BW5147 thymoma secrete two suppressor factors, TsF‐A and TsF‐E. The factors carry the same antigen‐binding chains but different major histocompatibility complex (MHC) chains (Aβ‐like and Eβ‐like, respectively). The TsF‐A suppresses the proliferation of A‐restricted, LDH‐B‐specific T helper (Th) cells. In this report we demonstrate that the addition of the TsF‐E (isolated on immunosorbent columns with Ek‐ or Jk‐specific antibodies) to the culture of LDH‐B‐primed B10.A(2R) lymph node cells turns the nonrespnder (suppressed) cultures into proliferating ones, and that this change is antigen specific. This enhancing effect occurs in the early phase of the cell culture; the factor has no effect when added 2 days after the initiation of the culture. Because pretreatment of the Ly‐2+but not of the Ly‐1+2−cells with TsF‐E induces responsiveness, it is very likely that the targets of the factor are the Ts cells or their precursors that belong to the Ly‐2+subset. An incubation period of about 4 h is necessary for the TsF‐E to expert its action. The enhancing effect of the TsF‐E is abrogated by monoclonal antibodies specific for Ekand Jkantigenic determinants. However, only some of the antibodies that retain the TsF‐E on the immunosorbent column neutralize the factor in a functional test. Antibody blocking studies also indicate that the MHC determinants involved in the interaction between the antigen‐presenting and the Ts cell during Ts cell activaton, and in the TsF‐E Ts cell interaction are either very similar or identical. We interpret the data as indicating that the Ts cells or their precursors recognize the TsF‐E with the same receptors as they use for the recognition of LDH‐B together with the Ekon the antigen‐presentign cells. The recognition of the TsF‐E inactivates the Ts cell so that proliferation of Th cells then occurs unhindered. Thus, the production of the TsF‐E may provide a feedback mechanism that regulates the activation of the Ts cells and,

ISSN:0014-2980    

DOI:10.1002/eji.1830140802

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractThe unusual anti‐mouse immunoglobulin (Ig) sensitization of a renal allograft recipient who was treated prophylactically with the anti‐T cell monoclonal antibody OKT3 (IgG2a) is reported. Whereas in most patients, the injection of OKT3 (5 mg/day, i.v. for 13 days) induces the rapid appearance of neutralizing anti‐OKT3 antibodies, the patient reported here did not show the signs of conventional anti‐OKT3 sensitization. High levels of circulating OKT3 persisted and no OKT3+lymphocytes reappeared during the whole treatment period. Moreover, no IgG or IgM anti‐OKT3 antibodies were detected at any time, using a specific enzyme‐linked immunosorbent assay. However, an atypical anti‐isotype response was evidenced in this subject whose Ig were shown by indirect fluorescence to bind to normal T cells coated with OKT3 or with other anti‐T cell murine monoclonal antibodies carrying the IgG2aisotype (no reactivity was observed with IgG1or IgG2bmolecules). The patient's Ig did not bind to normal T cells coated with F(ab')2fragments of OKT3 and did not inhibit the binding of OKT3 to its target antigen indicating that they reacted with the Fc fragment of the OKT3 molecule. Additionally, and probably explained by this unusual anti‐OKT3 response, the patient's Ig were shown to inhibit the phytohemagglutinin‐induced proliferation of normal lymphocytes, to bind under selectedin vitroconditions to normal T cells and lastly to enhance the antigenic modulation inducedin vitroby OKT3 on it

ISSN:0014-2980    

DOI:10.1002/eji.1830140803

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractMacrophage‐chemotactic factor (MChF)‐producing T cell hybridomas were established. These hybridomas produced MChF upon the specific antigenic stimulation with phosphorylcholine (PC)‐conjugated protein in the presence of I‐Ed‐positive antigen‐presenting cells. The hybridomas also secreted MChF after co‐culture with concanavalin A in the absence of antigen‐presenting cells. The MChF‐secreting hybridomas were positive for Kd, Dd, Lyt‐1.2 but negative for I‐Ad, Lyt‐2.2. The molecular weight of MChF produced by the hybridomas was 43000 and the factor was focused at pH 6.6‐6.8 in the chromatofocusing procedure. The MChF was protease sensitive but resistant to neuraminidase treatment, and it was stable by heating at 80°C for 15 min. The MChF‐producing hybridomas established in this study did not produce macrophage migration inhibitory factor (MIF), macrophage‐activating factor (MAF) or interleukin 2, suggesting molecular nonidentity between MChF and these lymphokines. The MChF‐producing T cell hybridomas reactive to specific antigens (PC) will be promising tools for analysis of molecular nature of MChF as well as molecular aspects of antigen

ISSN:0014-2980    

DOI:10.1002/eji.1830140804

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractHuman T lymphocyte clones (TLC) specific for diphtheria toxoid (DT) were isolated from a DR6/7 individual by cloning in soft agarin vivosensitized T lymphocytes. We report here the isolation and characterization of 3 of these clones by studying: (a) the kinetic of activation, (b) the surface phenotypes, (c) the fine specificity for one of the 2 DT chains and (d) the genetic restriction of the proliferative response by the haplotype DR7.Moreover, blocking studies of the proliferative response to DT by various immunochemically characterized anti‐HLA‐DR monoclonal antibodies indicate that, on the DR7 molecule, more than one Ia determinant may participate in the clonal DT proliferative response. By using human TLC of a defined specificity and well‐characterized anti‐DR monoclonal antibodies, such studies may help to define the functional repertoire of Ia molecules

ISSN:0014-2980    

DOI:10.1002/eji.1830140805

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractSchistosomula were recovered from the skin of mice following primary infections. On the surface of such “infecting schistosomula”, mouse C3 could not be detected by immunofluorescence. Subsequent incubationin vitrowith fresh mouse serum led to the effective deposition of mouse C3 on schistosomula only when they were recovered within a few hours but not after one or two days following infection.In vitrodeposited murine C3c was lost from i.v. injected schistosomula in the mouse circulation within one day as was human C3c. Infecting schistosomula exhibited a close to complete resistance to the lyticin vitroactivity of human complement. This resistance was complete in older parasites. It existed in spite of the presence of parasite‐bound human C9, which was detectable on all developmental stages of schistosomes following incubation in fresh, but not inactivated human serum. Lung schistosomula, 3‐week and 6‐week‐old schistosomes were resistant to cellular cytotoxicity upon incubation with fresh human serum and rat peritoneal exudate cells although cell adherence mediated by human C3b was demonstrated with lung worms. The data suggest that schistosomula may evadein vivothe lytic activity of complement and also complement‐mediated cellular cytotoxicity. Depending on the species of serum, this can be demonstratedin vitroby lack of opsonization or by resistance to lytic and cellular atta

ISSN:0014-2980    

DOI:10.1002/eji.1830140806

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractThe E receptor (binds sheep erythrocytes) is found on virtually all human T cells. Here we show that a monoclonal antibody 9.6, which recognizes and binds the E receptor, inhibited interferon‐γ production by human peripheral blood mononuclear leukocytes induced with the mitogens phytohemagglutinin, concanavalin A, Staphylococcal enterotoxin A and the monoclonal antibody OKT3. Metabolic activation (RNA and DNA synthesis) in human peripheral blood mononuclear leukocytes in response to mitogens was also sharply inhibited by 9.6. This inhibitory effect occurred early during the induction phase since 9.6 had much diminished inhibitory effects when added 15‐24 h after induction; peak IFN‐γ production and DNA synthesis occurred 3‐4 days post induction. An early event inhibited by 9.6 appeared to be interleukin 2 (IL2) receptor formation since: (a) the ability of mitogen‐stimulated peripheral blood mononuclear leukocytes to absorb IL2 was inhibited by 9.6, and (b) lines of T lymphocytes which already expressed IL2 receptors were largely resistant to the inhibitory effects of 9.6 on IFN‐γ production and DNA synthesis. The tumor promoters 12‐O‐tetradecanoyl phorbol‐13‐acetate and teleocidin largely reversed the inhibition by 9.6 of IFN‐γ production and metabolic activation induced by mitogens. A model for the control of IFN‐γ induction involving four receptors, those for mitogens, tumor promoter, IL2

ISSN:0014-2980    

DOI:10.1002/eji.1830140807

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractModulation and co‐modulation of membrane‐bound IgM and IgD and of I region‐encoded antigens (I‐A and I‐E) were studied by immunofluorescence with the use of monoclonal antibodies. The two sets of molecules displayed different ability to be redistributed, by divalent ligands: immunoglobulins could be easily redistributed, while this was not the case for I‐A and I‐E molecules. After short periods of activation, however, this property was found to change drastically: I‐region antigens were redistributed into polar caps, and immunoglobulins were modulated without clear polar redistribution.Cross‐linking and removal of one of the molecules always resulted in the modulation of at least one other, often two membrane molecules. Concomitantly, an additional molecule was expressed in higher amount. The results are compatible with the existence of specific interactions at the level of the B cell membrane, involving the four molecules in the order I‐A → IgM → I‐E → IgD. Such interactions, probably reversible in the unperturbed state, are likely to change in affinity when one molecule interacts with a ligand. The possible relevance of membrane interactions between immunoglobulin and class II antigens in the regulation

ISSN:0014-2980    

DOI:10.1002/eji.1830140808

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractThe combination of the phorbol ester 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) and the calcium ionophore ionomycin is synergistically mitogenic for human fetal and infant thymocytes as well as peripheral blood lymphocytes. Optimal mitogenic stimulation is achieved when TPA and ionomycin are used at doses of 0.5‐1 ng/ml and 0.5‐1 μg/ml, respectively.Phenotypic analysis and cell sorting show that the thymocytes responsive to the mitogen have a mature or medullary phenotype (T1+, T3+, T11+, T6−, HLA‐A,B++, [TdT]−); similarly in blood the T cell subsets (T11+, T4+and T11+, T8+) are selectively responsive to TPA‐ionomycin. Both activated lymphocytes and thymocytes express HLA‐DR antigens as well as activation antigens such as T9, T10 and T cell activation antigen. T cells activated by TPA‐ionomycin can be grown for periods of up to 50 days without addition of exogeneous interleukin 2. The observations may have implications for the membrane‐associated signals involved in T cel

ISSN:0014-2980    

DOI:10.1002/eji.1830140809

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractHeterologous anti‐mouse δ chain has been shown to induce T‐independent polyclonal B cell proliferation by 24 h after injection into mice and a T‐dependent polyclonal increase in the number of IgG‐secreting cells in spleen and lymph nodes 6 days after injection. The effect of anti‐δ on germinal center cells has been difficult to determine, however, since anti‐δ‐induced blast transformation of mantle zone cells makes it difficult to distinguish these cells from germinal center cells. To clarify the effect of anti‐δ on germinal centers, we stained lymph node sections from control and anti‐δ‐injected mice with peanut agglutinin conjugated to horseradish peroxidase which clearly differentiates the germinal center cells from other large and small lymphoid cells.For the first 5 days after i.v. injection of goat anti‐mouse δ, the germinal center volumes did not differ significantly from those of mice injected with control antibodies. On days 6 and 7 after injection, the lymph node germinal center volumes of anti‐δ‐treated mice increased on average over 10‐fold as compared to those of mice injected with an equal amount of control antibody. Thus, while anti‐δ antibody directly induced blastogenesis of mantle layer B cells, it appears to have little direct effect on germinal center cells. In contrast, rapid germinal center development is seen in anti‐δ‐injected mice during the T‐dependent phase of B cell activation and occurs simultaneously with the appear

ISSN:0014-2980    

DOI:10.1002/eji.1830140810

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY

摘要:

AbstractLines of rat T lymphocytes responsive to the basic protein of myelin (BP) or to the purified protein derivative ofMycobacterium tuberculosis(PPD) were inoculated i.v. into recipient rats. As reported previously, the anti‐BP line cells, but not the anti‐PPD line cells spontaneously accumulated in the central nervous system and caused encephalomyelitis. However, the anti‐PPD line cells could be induced to enter the brain and cause bystander encephalitis by intracerebral inoculation of PPD. Anti‐PPD or anti‐BP line cells could mediate delayed‐type hypersensitivity skin reactions or bystander arthritis elicited by specific antigen. The lines did not cause specific cytolysisin vitro. Susceptibility to delayed‐type hypersensitivity or bystander disease was long lasting in rats inoculated with anti‐PPD line cells, while rats inoculated with anti‐BP line cells were susceptible for only a few days. Thus, lines of T lymphocytes can mediate a variety of pathological reactions directed by the presence of specific antigen

ISSN:0014-2980    

DOI:10.1002/eji.1830140811

出版商:WILEY‐VCH Verlag GmbH    

年代:1984

数据来源: WILEY