摘要:

AbstractThe injection of mice with 800 μg of an affinity‐purified goat antibody to mouse IgD (GaMδ) induces early, T‐independent polyclonal increases in the expression of B cell surface Ia, and B cell size and DNA synthesis, as well as later, T‐dependent polyclonal increases in spleen cell number and Ig secretion. We have now studied the effects of varying the doses of injected GaMδ on all phases of B cell activation, as well as the effects of supplementing GaMG with varying quantities of normal goat IgG (GIgG). We have found that while 12.5 μg of GaMδ modulates most of the IgD from the surface of splenic B lymphocytes, it fails to activate these cells. Increases in the expression of B cell surface Ia are first seen when 50 μg of GaMδ is injected, while increases in B cell DNA synthesis usually require the injection of 200 μg of GaMδ and peak with doses of approximately 800 μg. Increases in splenic B cell number and DNA synthesis during the T‐dependent phase of GaMδ‐induced B cell activation are seen only in those mice that were injected with sufficient quantities of GaMδ to induce DNA synthesis during the T‐independent phase. Supplementing the dose of GaMδ injected with additional GIgG has no significant effect on B cell DNA synthesis or B cell number but dramatically increases polyclonal IgGlsecretion. Although mice which have been injected with 50 μg of GaMδ or with 800 pμ of GIgG alone have few polyclonal IgG1‐secreting cells, substantial increases in the number of IgG1,‐ secreting cells are seen in mice injected with 50 μg of GaMδ plus 750 μg of GIgG. GIgG and larger doses of GaMδ similarly act synergistically to increase polyclonal IgGlsecretion. In contrast to the induction of polyclonal IgGlsecretion, the stimulation of polyclonal IgM secretion requires the injection of mitogenic doses of GaMδ and is not enhanced by the injection of additional GIgG. These observations suggest that, in this model system, stimulatory signals that activate B cells through their surface Ig are limiting for the induction of polyclonal proliferation and IgM secretion, while the generation of T helper lymphokines that do not directly interact with B cells through their surface Ig may be more limiting for the sti

ISSN:0014-2980    

DOI:10.1002/eji.1830150402

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractA comparative analysis of responses between resistant and susceptible hosts revealed that DBN/2 mice, after treatment with variant surface coat glycoprotein (VSG) from virulent or avirulent African trypanosomes, developed splenomegaly as the result of a near‐doubling of the splenic cell population, had less polyclonal activation of B cells and were protected upon challenge with homologous trypanosomes. The susceptible C3H/Anf and C3W/HeJ mice on the other hand increased their splenic cell population by only 12%, had about twice the production of unelicited antibodies and were not immunized by the VSG treatments. This indicated that (a) proliferation of spleen cells during African trypanosomiasis may reflect an attempt to generate a specific and protective immune response and is not merely the result of polyclonal activation of lymphocytes; (b) production of unelicited antibodies is not merely a “bystander reaction” to the generation of antigen‐specific responses; and (c) polyclonal antibody production in response to VSG is not linked to the LPS gene. Nonspecific immunosuppression as measured in mitogen assays was not elicited by VSG in either resistant or susceptible mice, indicating that polyclonal lymphocyte activation and nonspecific immunosuppression are unlinked phenomena.Mice injected with VSG from either virulent or avirulent isolates at levels normally encountered by hosts during severe, acute infection developed the same degree of splenomegaly and production of unelicited (polyclonal) antibodies. Therefore, any differences in polyclonal activation of lymphocytes measured between mice with acutevs. chronic African trypanosomiasis can be attributed to quantitative and not qualitative differences

ISSN:0014-2980    

DOI:10.1002/eji.1830150403

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractThe possibility of the generation of secondary cytotoxic T lymphocyte (2oCTL) activity from alloantigen primed T cells by genetically homogeneous recombinant human interleukin 2 (G‐IL2) was analyzed. Not only purified IL2 by cell culture (C‐IL2) but also G‐IL2 induced 2oCTL activity from primed T cells generated in mixed lymphocyte culture. This induction process required RNA and protein synthesis, while DNA synthesis was not relevant. In parallel to the induction of 2oCTL activity, transition of the primed cells from the resting G1ato activated G1bhas taken place. 2oCTL activity was induced from nylon column‐purified primed T cells in the absence of accessory cells and also in the absence of Lyt‐1+T cells. Interferon‐y (IFN‐γ) induction was detected during the course of activation of alloantigen‐primed T cells into the cytotoxic state. When IL2 was absorbed, IFNγ in the culture supernatant did not induce 2oCTL activity. These results suggest that the IL2 molecule possessing T cell growth factor properties shares the nature of differentiation factor in terms of the activation of alloantigen‐primed T cells into cytotoxic state. The role of IFN‐γ producedin situfor this activation process awaits

ISSN:0014-2980    

DOI:10.1002/eji.1830150404

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractThe lectin leucoagglutinin has been used to induce reactivity to interleukin 2 (IL2) in unseparated spleen cells and in highly purified Lyt‐2+lymph node T cells. Recombinant human IL2 and various other IL2‐containing preparations, including con‐canavalin A‐induced spleen cell supernatant, were compared for their capacity to support DNA synthesis and cytotoxic activity. In contrast to published reports, we found that the capacity of all preparations tested was identical in both functional assays, if they were adjusted to the same IL2 titer. Our inability to detect a requirement for an externally added cytotoxic T cell differentiation factor could either mean that IL2 is sufficient for the promotion of both proliferation and differentiation in leucoagglutinin‐activated resting cytotoxic T cell precursors, or that under our experimental conditions, T cell differentiation factor is endogenously produced by Lyt

ISSN:0014-2980    

DOI:10.1002/eji.1830150405

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractUsing fluorescein‐labeled effector lymphocytes and tetramethyl rhodamine‐labeled target cells a cytofluorometric method is described for the detection and quantification of lymphocyte‐target cell cluster (conjugate) formation. Conjugation levels mea‐ sured by cytofluorography correspond well with those scored microscopically. The method has so far been used successfully to monitor conjugate formation by specifically sensitized cytotoxic T lymphocytes (CTL). In preliminary experiments it has been applied to nonspecific, lectin concanavalin A‐dependent conjugate formation by CTL, as well as to conjugates formed by hybridoma CTL. The procedure has potential application in other cell‐cell interactions, relevant to immunology as well as to c

ISSN:0014-2980    

DOI:10.1002/eji.1830150406

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractThe expression of the interleukin 2 receptor (Tac) on normal B cells and Epstein‐Barr virus‐transformed lymphoblastoid B cell lines is induced by the tumor promoter 12‐O‐ tetradecanoyl‐phorbol‐13‐acetate (TPA). The receptor on B cells is indistinguishable from that on T cells by serological and biochemical analysis. It is functionally active so that TPA‐induced B cells respond to interleukin 2 by increased DNA synthesis. These results suggest that the expression of Tac is not exclusively restricted to T cells and that interleukin 2 may play a role in B cell

ISSN:0014-2980    

DOI:10.1002/eji.1830150407

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractExperiments to test the relationship between the epitopes on a protein antigen recognized by T and B cells in their collaboration to produce antibody cannot rely solely on hapten‐carrier models. In the present work we usedE. coliβ‐galactosidase, a molecule whose tertiary and quaternary epitopes have been well characterized, as the model antigen. T helper cells were raised by stimulating mice with the intact or the denatured molecule or with any of several β‐galactosidase cyanogen bromide pep‐ tides. In a series ofin vitrohelper T cell assays we confronted the various T popula tions with B cells preimmunized with the native antigen, and we tested their capacity to help production of (a) binding antibodies and (b) antibodies directed to single conformational epitopes, characterized by their capacity to protect the enzyme from heat denaturation or to activate defective P‐galactosidase. According to our results, (a) equivalent T cell help can be provided by T helper cells primed with native or denatured antigen, even for the production of “conformational” antibodies; (b) one of the peptides (CB‐18) is most efficient in raising help for binding antibodies; and (c) two peptides (CB‐20 and CB‐21) rank highest in priming T helper cells for the even‐ tual production of protecting and activating antibodies, respectively. Thus, not every β‐galactosidase‐specific T helper cell is useful in providing help to B cells specific for any particular epitope on the molecule, but rather preferential pairings exist, possibly

ISSN:0014-2980    

DOI:10.1002/eji.1830150408

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractPolypeptides synthesized in a rabbit reticulocyte lysate system directed by mRNA from the T cell line LH8‐105, obtained by radiation leukemia virus‐induced transformation of hen egg‐white lysozyme (HEL)‐specific suppressor T lymphocytes, are able, when injected into mice, to specifically suppress the antibody response and delayed‐type hypersensitivity to HEL. The suppressive activity exerted byin vitrotranslated proteins appears to be independent from post‐translational modifications. Thesein vitrotranslated polypeptides display fine antigenic specificity in immunosup‐ pression and bind to HEL but not to the closely related ring‐necked pheasant egg‐ white lysozyme immunosorbents. Suppressive molecules obtained by cell‐free translation of LH8‐105 mRNA or by culture supernatant of LH8‐105 cells display, by gel filtration, a similar molecular

ISSN:0014-2980    

DOI:10.1002/eji.1830150409

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractWe present here the first report of a human helper/nducer T cell clone (F6) that specifically recognizes tetanus toxoid (IT) in the context of self‐major histocompati‐ bility complex (MHC) determinant(s) (HLA‐DR3), and in addition recognizes a specific but unrelated MHC determinant(s) in the absence of conventional antigen. Extensive subcloning insured that the cells were progeny of a single cell. Furthermore, removal of the cells proliferating to the alloantigen with bromodeoxyuridine and light removed cells responding to both TT plus self‐MHC and to the stimulating alloantigen, again indicating that F6 was the progeny of a single cell.The alloantigen recognized by this TT‐specific clone appears to be closely linked to HLA‐DR4 since cells from 13 of 14 HLA‐DR4+donors stimulated F6. An antiserum which recognizes HLA‐DR4, when added to cultures, blocked the alloreactivity of F6, and in addition blocked its proliferation to 'IT plus HLA‐DR3. Absorption of this antiserum with HLA‐DR4+cells or with IT‐pulsed HLA‐DR3+cells removed its capacity to inhibit the proliferation of F6. These results suggest that the antigen recognition unit on F6 is stimulated both by allodeterminants expressed on HLA‐DR4 cells and by TT plus HLA‐DR3. These moieties cross‐react at the T cell recogni‐ tion level a

ISSN:0014-2980    

DOI:10.1002/eji.1830150410

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractAn interaction between antigen and macrophage‐like cells which display I region gene products [antigen‐presenting cells (APC)] is necessary for activation of inducer T cell clones. The specificity of inducer cell activation has been found to be major histocom‐ patibility complex (MHC)‐restricted and antigen specific. This is thought to reflect formation of a ligand consisting of MHC class II gene products associated in some way with foreign protein.A panel of inducer T cell clones with different activation specificities and homogene‐ ous lines of APC expressing different MHC haplotypes was used to define this ligand. We isolated a product formed after interaction between antigen and APC expressing defined MHC products. This ligand binds only to the T cell clones that are specifically activated by the same antigen and APC as judged by tritiated thymidine incorpora‐ tion. The ligand is composed of two moieties: I‐A determinants and the foreign protein (“antigen”). Coelution and sequential precipitation studies of the two moieties indicate that the nominal antigen and MHC product are tightly linked. The implications of these findi

ISSN:0014-2980    

DOI:10.1002/eji.1830150411

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY