摘要:

AbstractThe viral antigen specificity of primary cytotoxic T cell responses (CTL) of H‐2b, H‐2k, H‐2q, H‐2s, H‐2fand some H‐2‐recombinant mice against lymphocytic choriomeningitis virus (LCMV‐WE isolate) as well as the specificity of some CTL clones and T cell lines was defined on target cells infected with vaccinia‐recombinant virus expressing nucleoprotein (Np) or glycoprotein (Gp). Np was recognized together with H‐2q(Dq), H‐2d(DLd), H‐2sand H‐2b(Db). Gp specificity was restricted to H‐2fand H‐2b(Kband Db); H‐2k‐restricted CTL anti‐LCMV responses were neither Gp nor Np specific.The anti‐viral protective immunity induced by vaccinia‐Gp or vaccinia‐Np recombinants was evaluated in mice.In vivoprotection was T cell mediated by class I restricted Ly‐2 T cells; it correlated well with the CTL specificity definedin vitro. Some of the CTL‐nonresponder H‐2 allele plus Np or H‐2 plus Gp combinations were, however, protected to variable and low degrees by vaccinia‐recombinant viruses, indicating that anti‐viral protection is a more sensitive readout for CTL activity than thein vitroassay. For example, B10.D2 H‐2dmice generated measurable CTL responses only to Np; after immunization with a vaccinia‐Np recombinant, LCMV titers were 104times lower in spleens than in vaccinia‐primed controls. Although vaccinia‐Gp‐immunized BALB/c mice revealed no CTL activityin vitro, they nevertheless had 102times lower LCMV titers in spleens than controls. Anti‐viral protection, particularly in low‐responder combinations, was usually short‐lived and diminished after 3 weeks. In a high‐responder situation, protection was of a longer duration (>8 weeks). Vaccination with vaccinia‐Np or Gp recombinants protected mice against lethal T cell‐mediated lymphocytic choriomeningitis induced by LCMV or prevented the local footpad swelling reaction; thesein vivoeffects were H‐2 depen

ISSN:0014-2980    

DOI:10.1002/eji.1830190302

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractB cells from bursa of Fabricius of newly hatched chickens are able to reconstitute the B cell compartment of chemically bursectomized chickens. The resulting B cell chimerism can be detected with monoclonal antibodies against donor B cell alloantigen. Chimeric chickens accept donor‐type skin grafts and are unresponsive to donor major histocompatibility complex (MHC) antigens in graft‐vs.‐host splenomegaly assay and mixed lymphocyte reaction. To study the capability of B cells to induce tolerance to selected MHC antigens, we transplanted class I or total MHC‐incompatible bursa cells into cyclophosphamide‐treated recipients. The recipients of class I or total MHC‐incompatible bursa cells were equally tolerant of donor‐MHC antigens. To further analyze the mechanisms of tolerance to class I antigensvs.total MHC, spleen cells from tolerant chickens were transferred to irradiated, histocompatible secondary hosts. The secondary recipients were also unresponsive to bursa cell donor‐strain MHC antigens. However, if the chimeric B cells were depleted before the spleen cell transfer, the transfer of tolerance to total MHC was severely inhibited. Instead, most recipients of B cell‐depleted spleen cells tolerant of class I antigens were still tolerant of bursa cell donor MHC. Our results indicate differences in the transferability of tolerance to class I antigensvs.entire MHC, although in primary recipients of bursa cells the tolerance is similar. These data suggest that a mechanism that is not dependent on the presence of donor cell chimerism contributes to the maintenance of tolerance to donor class I antigens. The transfer of tolerance to total MHC disparity requires the presence of chimeric cells indicating that donor alloantigen expression is needed for induction of tolerance in th

ISSN:0014-2980    

DOI:10.1002/eji.1830190303

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractA DP serological allospecificity was identified using125I‐labeled preparations of HLA class II molecules isolated from cells of HLA homozygous typing cell lines, SLE (DRw6, DQw1, DPw3) and WT46 (DRw6, DQw1, DPw2), and depleted of DR molecules by absorption with an anti‐DR monoclonal antibody. The specificity, provisionally called WT, was carried by class II molecules possessing the characteristics of DP molecules on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, and detected primarily in DPw1, DPw3 and DPw5 cells and exceptionally in some DPw2 cells including WT46 and DPw4 cells on a large panel of DP‐pretyped B cell lines mostly derived from the 10th International Histocompatibility Workshop B cell reference panel. It was apparently allelic to another DP serological specificity BUT previously defined on DP molecules isolated from cells of DPw2 HLA deletion mutant cell line LCL 721.82. On the same cell panel, the BUT specificity was negative in all DPw1, DPw3 and DPw5 cells, and positive in all DPw2 and DPw4 cells and also in DPw2B and DPw4B cells except the cells typed WT. This DP association pattern was similar to that of the known allelic sequences, GGPM and DEAV, in DP ß F segment, one of the six variable segments in the second exon of DP ß gene. Thus, genomic DNA from 22 B cell lines pretyped for BUT and WT specificities were enzymatically amplified for the second exon of DP ß gene by the use of locus‐specific oligonucleotide primers and hybridized with32P‐labeled oligonucleotide probes corresponding to the F segment sequence variations. This oligonucleotide typing showed perfect one‐to‐one correlation with the BUT and WT serological typing. The typing also revealed that WT46 cells, although typed DPw2, have the DEAV sequence common to D

ISSN:0014-2980    

DOI:10.1002/eji.1830190304

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractImmunization of mice with 2,4‐dinitrophenyl‐Bordetella pertussis(DNP‐BP) failed to induce anti‐DNP IgE responses. Administration of DNP‐BP induced, however, the formation of anti‐DNP IgE B memory cells, as demonstrated by adoptive transfer. Furthermore, mice pretreated with DNP‐BP and primed with 2 μg DNP‐ovalbumin (OA) in alum 2 weeks later produced high day‐7 anti‐DNP IgE levels. These subsided to near undetectable levels by day 12–14. The transient expression of serum IgE levels was accompanied by normal levels of anti‐DNP IgG. The anti‐OA response induced as a result of priming with DNP‐OA in alum was not affected by pretreatment with DNP‐BP. IgG subclass analysis revealed that mice pretreated with DNP‐BP had elevated levels of IgG2aand reduced levels of IgG1as compared to control (TNP‐keyhole limpet hemocyanin‐pretreated) mice. Treatment of mice with an anti‐interferon‐γ monoclonal antibody, shortly after immunization with DNP‐BP, not only reduced anti‐DNP IgG2alevels, but prevented the sharp anti‐DNP IgE decline that occurred after priming with DNP‐OA in alum. These results suggest that DNP‐BP‐induced interferon‐γ production modulates I

ISSN:0014-2980    

DOI:10.1002/eji.1830190305

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractHLA antigen‐loss mutants and class I gene transferents were used to analyze the influence of class I expression on natural killer (NK) cell‐mediated lysis. Only HLA antigen‐loss mutants that had lost expression of either HLA‐A and HLA‐B antigens (mutant .184) or of HLA‐A, B and C antigens (mutant .221) were distinctly susceptible to NK‐mediated lysis. Mutants with reduced expression of class II antigens but unaltered expression of class I antigens remained resistant to NK lysis. A direct demonstration of the effect of class I antigen expression on human cells was made by analyzing a variety of gene transferents of the HLA‐A, B, C null mutant .221 expressing only one transferred HLA‐A, B or C gene. These results specifically show that expression of class I antigens, with a possible preferential effect of HLA‐B expression, reduces the susceptibility of mutant .221 t

ISSN:0014-2980    

DOI:10.1002/eji.1830190306

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractWe report on the molecular characterization of the heavy (H) chain variable (V) region of two murine autoantibodies reacting with a conventional self antigen, thyro‐globulin (Tg), originated from unimmunized/unstimulated neonatal mice (clone B10H2) and from an adult hyperimmunized mouse (clone 62), respectively. Serologically, both hybridoma antibodies express the same idiotype (Id). By cloning and sequencing we demonstrated that their VHregions are encoded by identical VDJ gene elements including the VD and DJ joints. This VHbelongs to the VH7183 gene family, the most 3′‐end proximal family in the murine genome. The D segment is unique and only 50% similar to any murine D segment. The J segment utilized is germ‐line JH4. The cloned DNA rearrangement was transfected into the J558L myeloma cells and the secreted antibody was found to express the reference Id on the H chain, hence proving that the productive VDJ rearrangement had been identified. These results show that a spontaneously arising and an antigen‐induced autoantibody use an identical VDJ gene rearrangement and that after hyperimmunization somatic mutation did not occur. The significance of this finding with respect to ontogeny of the B cell repertoire is

ISSN:0014-2980    

DOI:10.1002/eji.1830190307

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractWe have examined the immune repertoire and immune response of a mouse that carries transgenes for a μ heavy chain and ϰ light chain. The expression of these genes is under the regulation of their own controlling elements. The transgenes are expressed early in ontogeny and are easily detectable from day 13 of gestation onwards. The pre‐B cells seem to function normally as they generate IgM‐secreting colonies at normal frequencies. Colonies show predominantly the transgenic specificity. Expression of the transgenes is not limited to B cells since around 10%–20% of peripheral T cells and 50% of thymocytes express the μ transgene as an intracellular protein. Ectopic expression of ϰ was not seen. The spleen size of the transgenic mouse is decreased by around 20%; this reduction is largely caused by a reduction of the B cell pool. Almost all B cells express the transgenes, only 30% co‐express endogenous heavy chain genes and all co‐express endogenous light chain genes. Serum Ig levels for IgM and IgA were normal, 20% of the IgM consist of the transgenic product. Serum IgG levels were decreased. T cell functions (helper and cytotoxic) were normal. Immune responses to conventional antigens were impaired, especially in the early phases of the immune response, but after boosting they were virtually normal, except for IgG3which remained low. Primary antibody reponses to T cell‐independent antigens of the class II type (bacterially related antigens) were absent, although precursor frequencies for these antigens were within the expected range. The significance of this finding, as it relates to allelic exclusion of Ig gene

ISSN:0014-2980    

DOI:10.1002/eji.1830190308

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractA patient is described, having Richter's syndrome and immunodeficiency with hyper IgM, who developed suppressor T cell lymphoma (CD3, CD4‐, CD8) following untreated helper‐suppressor T cell chronic lymphocytic leukemia (CD3, CD4, CD8). The neoplastic T cells in both malignancies expressed interleukin (IL) 2 receptors but were deficient in typical CD2 and CD5 pan T antigens. Additionally, a large percentage of malignant lymph node T cells expressed HLA‐DR activation antigens.In vitroimmunoglobulin‐production experiments demonstrated that the patient's leukemic blood T cells had an excess helper function for IgM synthesis but a suppressor function for IgG and IgA synthesis by normal B and T cells. The leukemic blood T cells demonstrated a poor response to phytohemagglutinin (PHA). A defect in IL 2 receptor expression was evident in PHA‐stimulated leukemic blood T cells. Of interest was the observation that PHA stimulated the induction of a novel CD3, CD4‐, CD8 T cell subset from patient's CD3, CD4, CD8 leukemic blood T cells. These PHA‐induced CD3, CD4‐, CD8 T cell subsets produced an elevated proliferative response to PHA and concanavalin A, had a helper cell function for IgM synthesis and produced highly elevated

ISSN:0014-2980    

DOI:10.1002/eji.1830190309

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractThe selective migration of mucosal‐derived lymphoid blasts to other mucosal organs is taken to be an essential part of the common secretory immune system. In rats, proliferating lymphoid cells from mesenteric lymph nodes (mLN) and peripheral lymph nodes (pLN) were labeledin vitrousing two different techniques, in order to test the hypothesis that the mucosa of the male genital tract is a preferential site for mLN lymphoid blasts to home to. A low but significant migration to male genital organs was found, but with no difference between blasts from pLN and mLN. Thus there is no evidence to include the male genital tract in the common mucosal secretory immune system.Recirculating lymphocytes from the thoracic duct entered the male genital organs with a similar distribution to the pattern of lymphoid blasts. There is probably an exchange between these immigrating lymphocytes and the different subsets, which are localized in the epithelium (T suppressor) and interstitial tissue (T helper) in male genital organs. The lymphoid cells in the male genital tract might play an important role in the immune function of seminal fluid and in sexually transmissible disease

ISSN:0014-2980    

DOI:10.1002/eji.1830190310

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractCross‐linking of surface Ig receptors (sIg) by mitogenic forms of anti‐Ig antibodies (e.g.F(ab′)2fragments of rabbit anti‐Ig) causes the rapid, and prolonged breakdown of phosphatidylinositol 4,5‐bisphosphate. This response involves an unidentified guanine nucleotide regulatory protein (termed Gp), which couples sIg to the polyphosphoinositide‐specific phosphodiesterase. Intact (IgG) rabbit anti‐Ig antibodies, which co‐cross‐link sIg and Fcγ receptors on B cells, only induce short‐lived inositol phospholipid breakdown and abortive B cell activation. We show here that in permeabilized B cells intact anti‐Ig inhibits the reconstituted breakdown of inositol phospholipids given by a combination of F(ab′)2anti‐Ig and the non‐hydrolyzable GTP analogue guanosine‐5′‐O‐(3‐thiotriphosphate) (GTPγS), but not the basal stimulation of Gpinduced by GTPγS alone. These results therefore indicate that cocross‐linkage of sIg and Fcγ receptors on B cells uncouples the antigen receptors from the associated G protein, but does not affect coupling between Gpand the phosphodiesterase. These observations therefore provide further insight into the mechanisms whereby engaging Fc receptors on B cells, by antigen‐antibody complexes for example, cou

ISSN:0014-2980    

DOI:10.1002/eji.1830190311

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY