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E Kölsch

Publications and source records attributed to E Kölsch.

At least 37 records · Page 2Linked to original sources
PubMed1995

Isotype-associated recognition of allergen epitopes and its modulation by antigen dose.

The existence of competing and blocking IgG antibodies and their interrelationship with IgE antibodies was investigated in the IgE immune response of CBA/J mice to bee venom phospholipase A2 (PLA2) and keyhole limpet haemocyanin (KLH). Minute doses of antigen induced high titres of both IgE and IgG antibodies, whereas large doses elicited high IgG responses but only weak IgE antibody titres. Immunization with minute doses of antigen led to the production of antibodies with class-associated epitope specificities (designated epitopes G for IgG and E for IgE antibodies), and therefore no competition was observed. For IgG antibody production, G epitopes were immunodominant and IgG antibodies directed to E epitopes were produced only after immunization with an increased immunogen dose. Under this condition IgG antibodies recognizing the E epitopes acted as blocking antibodies competing with IgE antibodies for binding to E epitopes, the immunodominant epitopes for the IgE response. The data demonstrate the existance of distinct immunodominant antigenic determinants for IgE and IgG antibodies on PLA2.

Animals↗
PubMed1994

T helper target cell DNA fragmentation through a CD4-positive T suppressor cell clone inducing specific unresponsiveness.

The CD4-positive bovine serum albumin (BSA)-specific Ts cell clone BVI/5 from a CBA/J mouse tolerized to low doses of BSA induces specific unresponsiveness in the T helper (Th) cell population. Tolerance induction can be measured in vitro in proliferation assays using specific Th cell clones or antigen-primed lymph node cells (LNC) and determined in vivo by the failure to produce hapten-specific antibodies. Using the BSA-specific Th cell clone 83/1 as a target one observes in addition 51Cr-release in a 16-hr long-term assay but finds no effect in a typical 6-hr T cell cytotoxicity test. BVI/5 Ts cells do not produce interleukin-2 but otherwise express a Th1 profile. The suppression of proliferation of 83/1 Th cells is partly due to interferon-gamma (IFN-gamma). But lysis of 83/1 Th cells as well as suppression of BSA-specific LNC proliferation needs direct cell contact between BVI/5 Ts cells and their targets. Cell lysis and suppression of LNC cannot be simulated by IFN-gamma, by the combination of IFN-gamma and TNF, or by BVI/5 supernatants. Thus mediators cannot account for specific suppression by BVI/5 Ts cells in polyclonal in vitro responses from LNC and are probably not responsible for the induction of in vivo unresponsiveness. Instead the data show that BVI/5 Ts cells induce apoptosis-like DNA fragmentation in cloned BSA-specific 83/1 Th cells and in LNC from BSA-primed mice. Apoptosis can also be visualized as chromatin condensation in the LNC population. Macrophages have been excluded as targets. It can further be demonstrated that BVI/5 Ts cells express perforin and granzyme A on activation. Thus they are equipped with the effector molecules for target cell destruction. We consider BVI/5 Ts cells to be representative of a regulatory T cell inducing specific unresponsiveness in peripheral lymphoid organs.

Animals↗
PubMed1994

Epitope-dependent nonreciprocal regulation of IgE and IgG2a antibody formation.

The antigen dose-dependent production of IgE versus IgG2a antibodies has been investigated using keyhole limpet hemocyanin (KLH) and bee venom phospholipase A2 (PLA2) as antigens. Repeated injections of minute doses (0.1 microgram/mouse) of KLH into CBA/J mice lead to relatively high titers of IgE antibodies which are gradually reduced in animals that had received higher doses of antigen. In contrast, the IgG2a antibody titers are inversely correlated, resulting in low titers after repeated injection of 0.1 microgram KLH and high titers after repeated doses of 10 micrograms/mouse. With PLA2 as antigen, one finds a comparable dose-dependent downregulation of IgE antibody production. In contrast to the response to KLH, there is, however, only a marginal IgG2a response at all doses tested, and no dose-dependent increase can be found. The data show that an inverse regulation of IgE and IgG2a responses is not mandatory. Instead there seems to be an additional regulation dictated by antigen epitopes.

Animals↗
PubMed1993

Characterization of idiotype-specific I-Ed-restricted T suppressor lymphocytes which confine immunoglobulin class expression to IgM in the anti-alpha (1- > 3) Dextran B 1355 S response of BALB/c mice.

The humoral immune response of conventionally raised BALB/c mice to the so-called "thymus independent" antigen alpha (1- > 3) Dextran B 1355 S (Dex) is predominantly of the IgM class. The response is further characterized by Igha allotype linkage and the dominance of the public idiotypes (Id) J558 and MOPC 104. In germfree raised BALB/c and in BALB/c nu/nu mice immunized with the same antigen an additional IgG response of the public Id is observed. Analysis of the regulation of the class expression reveals existence of specific Ts cells in euthymic mice which must have been activated pre- or perinatally by exposure to environmental bacterial antigens. They permit or enforce differentiation of Dex-specific B cells into B gamma memory cells without allowing further development into IgG producing plasma cells. An analogue of these splenic Ts cells has now been cloned and identified as an I-Ed restricted Id-specific T cell with exactly the properties ascribed above to the splenic Ts cells. This paper describes phenotypical and functional properties of the Ts cell clone 178-4. It evaluates this clone's role in controlling efficient anti-bacterial IgM-mediated immunity under conditions where a class switch to IgG antibody production is actively suppressed; possibly as a measure to avoid hazardous autoimmune reactions on the basis of crossreaction and antigenic mimicry between polysaccharide antigens.

Amino Acid Sequence↗
PubMed1992

Lymphokine profile and activation pattern of two unrelated antigen- or idiotype-specific T suppressor cell clones.

Two T suppressor (Ts) clones of different specificity have been analyzed for their lymphokine spectrum. BVI/5 is an I-Ek-restricted bovine serum albumin (BSA)-specific Ts cell clone from a CBA/J mouse tolerized by low doses of BSA. It affects directly or indirectly the function of BSA-specific T helper (Th) cells. The Ts cell clone 178-4 from a BALB/c mouse is I-Ed restricted and recognizes the public J558 Id on B cells. It prevents alpha(1----3)dextran B 1355S (Dex)-specific IgG antibody production and drives Dex-specific J558 idiotype-bearing B cells into an anergic B IgG memory cell state. Both Ts cell clones thus cause specific suppression, yet in different experimental systems using different effector mechanisms. Upon stimulation with concanavalin A or fixed CD3-specific monoclonal antibody, both clones produce high levels of interferon (IFN)-gamma and tumor necrosis factor (TNF) but in contrast to Th1 cells no interleukin (IL)-2. Both clones produce low levels of IL-3 and IL-6 but no IL-4, IL-5 and IL-9. Furthermore, unlike Th2 cells, both clones do not respond to IL-1. The mechanism of the idiotype-specific induction of anergy in Dex-specific B IgG memory cells by 178-4 Ts cells is not yet understood. BVI/5 Ts cells suppress in vitro the BSA-specific proliferation of the BSA-specific Th cell clone 83/1, as well as the response of BSA-primed CBA/LN cells. Whereas the suppressive effect on 83/1 cells is due to IFN-gamma alone the suppression of BSA-specific lymph node cells can be simulated neither by IFN-gamma nor the combination of IFN-gamma and TNF. Thus these mediators cannot account for the antigen-specific suppression by BVI/5 Ts cells in polyclonal in vitro responses from lymph node cells and probably not for the induction of in vivo unresponsiveness.

Animals↗
PubMed1991

T cell receptor alpha and beta gene expression in a murine antigen-specific T suppressor lymphocyte clone with cytolytic potential.

The composition of alpha and beta TCR genes was analyzed in a murine BSA-specific Ts cell clone with cytolytic potential. The isolated poly(A)+ mRNA from Ts cell clone BVI/5 was used to construct a cDNA library in the bacteriophage lambda gt11. Full-length cDNA clones specific for TCR alpha and TCR beta genes have been detected and isolated by hybridization with specific oligonucleotide probes. The functional rearranged TCR alpha gene is composed of a member of the V alpha 1 family, the junctional gene J alpha TT11 and C alpha. The gene segments V beta 13, D beta 2.1, J beta 2.4, and C beta 2 form the functional rearranged TCR beta gene. Furthermore, a nonfunctional TCR alpha gene transcript has been detected, where a V alpha 8 gene is rearranged to a so far not described J alpha gene segment (J alpha BVI). A stop codon in its junctional region is responsible for this non-functional transcript. By using Southern blot analysis, the described rearranged TCR genes can be detected in the J alpha junctional region and in the J beta 2 cluster on the genomic DNA level. Immunoprecipitation studies with the KT3 anti-CD3 mAb and flow microfluorimetry analysis with the H57-597 anti-TCR-alpha/beta mAb show that TCR/CD3 complexes are synthesized and expressed on BVI/5 Ts cells. Taken together, the cDNA sequencing data, the protein studies, and the specificity of Ag recognition demonstrate that the BVI/5 Ts cell clone not only transcribes the TCR alpha and beta genes but also expresses a functional BSA-specific receptor.

Amino Acid Sequence↗
PubMed1991

Differences in the induction of tumorspecific T suppressor lymphocytes among the peritoneal exudate cells in histocompatible BALB/cAnPt and BALB/cJ mouse sublines.

The BALB/c inbred strain of mice exists in several sublines, two of which are of special interest to tumorimmunologists. BALB/cAnPt mice develop plasmacytomas upon intraperitoneal injection of mineral oil in 61% of the animals. BALB/cJ mice on the other hand are relatively resistant and only a few animals develop tumors. The cellular immune response of BALB/cAnPt mice towards the transplantable plasmacytoma ADJ-PC-5 is characterized by the dominance of specific T suppressor (Ts) lymphocytes, when an immunization protocol is used which mimics some aspects of early stages of tumorigenesis by increasing exponentially the antigenic tumor load. Application of this in vivo induction protocol for Ts cells reveals that ADJ-PC-5-specific Ts cells capable of suppressing the generation of an in vitro cytotoxic response can be induced in BALB/cAnPt but not in BALB/cJ mice. No subline difference could be found when specific Ts cells were induced in vitro. The data point towards a subline difference of in vivo cell interactions rather than T cell repertoire composition.

Animals↗
PubMed1991

Antigen dose-dependent regulation of B epsilon-memory cell expression.

The data presented in this study document that the phospholipase A2 (PLA2)-specific IgE antibody response in high responder CBA/J mice is solely dependent on the antigen dose used for immunization. Repeated injections of minute doses (MD) of antigen (0.1 microgram/mouse) induce a persisting high level of PLA2-specific IgE antibody titer, whereas large doses (LD) (10 micrograms/mouse) induce a persisting low level of IgE. The IgG antibody titers are the same under both conditions. The low level IgE immune status induced by repeated LD is irreversible and cannot be boosted by MD. In contrast a single LD primes for a secondary IgE response which can be recalled by MD. A high level of PLA2-specific IgE antibodies induced by MD can be downregulated by a single intervening LD of antigen. A low level IgE immune status can be transferred with spleen cells of mice immunized with LD into naive syngeneic recipients, which then fail to mount a high level IgE response upon injection of MD of antigen. The experiments reveal two countercurrent processes, induction of B epsilon-memory cells after a single LD and additional activation of a persisting IgE-specific cellular suppression mechanism after repeated LD of antigen. These properties make the system suitable for the analysis of cellular interactions and of potential desensitization protocols.

Animals↗
PubMed1991

Cremophor EL as an adjuvant affecting immunoglobulin class switch in the immune response to the thymus-independent antigen alpha(1- greater than 3) dextran B 1355 S.

The humoral immune response to the so-called thymus independent antigen dextran B 1355 S in conventionally raised BALB/c mice consists solely of IgM antibodies. Expression of IgG anti-Dex antibodies in these mice is prevented by pre- or perinatally activated idiotype-specific T-suppressor lymphocytes. IgG B-memory cells nevertheless develop during the course of immunization, but are arrested in an anergic state. In the presence of Cremophor EL the induction of this anergic state is inhibited and the immune response shifts fully to an IgG anti-Dex response.

Adjuvants, Immunologic↗
PubMed1990

Regulation of the anti-alpha(1----3) dextran IgG antibody response of BALB/c mice by idiotype-specific T suppressor lymphocytes.

The immune response of BALB/c mice against the so-called thymus-independent bacterial Ag alpha(1----3) dextran (Dex) is restricted to the expression of few major idiotypes (Id). It is furthermore under the control of T lymphocytes which regulate the isotype expression in such a way that they prevent anti-Dex IgG antibody production upon immunization. At the same time these T cells are part of a regulatory system for Dex-specific B cell memory formation. The underlying Ts cell activity has previously been analyzed by using euthymic and athymic congenic animals. Now we have isolated CD4-positive Id-specific T cell lines and clones which by several criteria are representatives of the above Ts cells. They inhibit in vitro proliferation and antibody secretion of Dex-specific hybridoma B cells. They prevent Id-restricted in vivo IgG anti-Dex antibody formation in T cell-reconstituted BALB/c nu/nu mice. At the same time they enforce, again Id-specific, accumulation of Dex-specific B memory cells. As has been shown previously under the influence of splenic Ts cells, these B memory cells are arrested in the original host but can be expanded and activated for anti-Dex IgG antibody formation upon adoptive transfer into X-irradiated allotype congenic nonresponder BALB.Ighb mice. The data show that the regulatory influence of T cells on the anti-Dex response is Id specific. It can now be studied by means of cloned Ts cells.

Animals↗
PubMed1989

Establishment and characterization of an Epstein-Barr virus transformed cell line with strong phagocytic activity.

An immunoglobulin M (IgM)-positive cell line, Ms 28, apparently spontaneously transformed by Epstein-Barr virus (EBV) was established from peripheral blood cells of a patient with immature myeloblastic leukemia. It has been characterized according to phenotype, cytochemistry, and membrane antigen pattern. The cell line expresses lymphoid markers like CD 19, CD 22, and CD 30 and synthesizes and secretes IgM. Monocyte markers CD 11c, CD 14, and CD 15 are absent. Neither interleukin-1 (IL-1), nor tumor necrosis factor (TNF-alpha) are produced. But Ms 28 cells show strong phagocytic activity and engulf Latex particles and sheep RBCs (SRBCs) that need not to be opsonized. The phagocytic activity can be inhibited by chloroquine. Both phagocytosis and EBV nuclear-antigen (EBNA) expression can be observed in one and the same cell. Ms 28 cells might be useful to study immunologic activities like antigen processing and presentation.

Antigens, Differentiation↗
PubMed1988

A comparison of the IgG isotype expression in the so-called thymus-independent immune responses to alpha(1----3) and alpha(1----6) dextran.

This paper presents data on the IgG antibody response against two "thymus-independent" dextran (Dex) antigens from Leuconostoc mesenteroides, alpha(1----3) Dex B 1355S and alpha(1----6) Dex B 512F in BALB/c and C57BL/6 mice, which are considered to be responders or low responders to the respective antigen. The data point toward three common rules governing the two anti-Dex responses despite immunogenetic and antigenic disparities: (1) age dependency of the IgG isotype regulation of the response; (2) down-regulation of IgG isotype expression by T cells; and (3) individually determined preposition for IgG isotype formation in a given animal.

Aging↗
PubMed1988

Specific in vivo suppression of lymph node cell proliferation and humoral immune responses by cloned antigen-specific T suppressor cells.

Two BSA-specific Ts cell clones have been isolated from CBA/J mice tolerized by low doses of BSA. Together with one Ts cell clone isolated from an immune animal, they have recently been characterized with regard to phenotypes and in vitro functions. In the present report the in vivo effector functions of two of them (Ts cell clones BVI/5 and HF1.MS) are described. BSA-primed lymph node cells from CBA/J mice, which had received BVI/5 or HF1.MS Ts cells at the time of immunization, do not respond to a subsequent in vitro antigenic challenge. A human gamma-globulin (HGG)-specific lymph node cell proliferation is not influenced. BVI/5 Ts cells injected into mice at the time of priming with fluorescein (Flu)-conjugated BSA or Flu-HGG inhibit the humoral anti-Flu-response in Flu-BSA-primed animals. The anti-Flu-response in Flu-HGG-primed animals is only marginally affected by BVI/5 Ts cells. The data show that it is possible to induce immunologic unresponsiveness at the humoral level by reexposing in vitro propagated Ts cell clones to their syngenic in vivo environment.

Animals↗
PubMed1988

Multidirectional interactions in vitro between lymphoid cells from Mls-disparate strains.

Chromosome 1 of the mouse carries a number of genes for alloantigens which can be recognized by T cells, among those the mixed lymphocyte stimulation (Mls) locus and the lymphocyte stimulating determinant (Lsd) locus have been described. The Relationship between the antigens coded for by these two loci has been further analyzed using a B10.BR anti C3H/Tif T cell clone E11. Segregation analysis was done with 167 individuals from backcrosses of (BALB/c (Mlsb, Lsd-) x DBA/2 (Mlsa, Lsd+] F1 animals into BALB/c mice. The analysis of the backcross data and of a limited number of recombinant inbred (RI) strains did not allow the segregated of the two loci, despite the fact that stable clusters were obtained in cluster analysis of the segregation data. The reasons for this failure are discussed. Parallel to the genetic analysis, we have studied the functional properties of the E11 T cell clone. First, there is the proliferation of the E11 T cells upon stimulation by macrophages or B cells of Mls-disparate stimulator strains. Second, there is an induction of differentiation of B cells of stimulator strains, requiring the direct interaction between E11 T and stimulator B cells. Third, there is an inhibitory influence of E11 T cells on the production of a mediator by Mls-disparate spleen cells presumably by their macrophages. We propose that the Mls antigen is a receptor regulating macrophage differentiation and transmitting a signal influencing the production of a mediator. This signal could be either the down regulation of the production of a stimulatory monokine or the induction of the production of an inhibitory monokine. Our presented data demonstrate that the anti Mls response is more complex than hitherto anticipated. It involves a multidirectional interaction between the Mls-disparate cell partners.

Animals↗
PubMed1988

Production of gamma interferon in Mls disparate interactions.

The murine T-cell clone E11 isolated from a primary H-2k histocompatible one-way mixed lymphocyte culture of B10.BR anti C3H/Tif spleen cells was used to study multidirectional interactions in strong stimulatory Mls disparate responses. Several parameters have recently been studied, and proliferation of T cells upon stimulation by macrophages or B cells of Mls-disparate stimulator cells, induction of differentiation of B cells of stimulator strains but inhibition of their macrophage differentiation, and the inhibition by E11 T cells of the production of a mitogenic mediator by Mls-disparate spleen cells have been found. As shown in this paper, these phenomena can be explained by an Mlsa, d, e specific induction of gamma-interferon (IFN-gamma) production in the responder B10.BR (Mlsb) E11 T cells. It is suggested that IFN-gamma, as a regulator of feedback mechanisms plays a critical role in Mls disparate T-cell stimulation.

Animals↗
PubMed1988

Modulation of cellular anti-tumour responses by tumour-specific T suppressor lymphocytes.

Tumour-specific Ts cells, induced by a protocol which simulates early stages of tumourigenesis in BALB/c mice by the syngeneic plasmacytoma ADJ-PC-5, suppress the generation of specific cytotoxic T lymphocytes (CTL) in a primary in vitro mixed lymphocyte tumour culture (MLTC) of BALB/c spleen cells against ADJ-PC-5. The influence of these Ts cells on the generation of non-specific killer cell activity has now been analysed. The data show that non-specific killer cells generated during in vitro MLTC lyse both ADJ-PC-5 and YAC-1 cells. They are different from tumour-specific CTL as shown by cold target inhibition experiments and on the basis of their different phenotype. The generation of non-specific killer activity during MLTC can be completely suppressed by ADJ-PC-5 specific Ts cells. Activation of non-specific killer cells by recombinant interleukin-2 (r IL2) alone is not influenced by these Ts cells. The in vitro data are best explained by assuming that the target for suppression are ADJ-PC-5 specific T helper cells. Their inactivation will result in depletion of IL2 in the culture, which is required to activate non-specific killer cells. Prevention of activation of specific and non-specific killer cells in vitro by activated tumour-specific Ts cells in the presence of the tumour, suggests that similar mechanisms might operate in vivo and that inactivation of tumour-specific T helper cells might be of central relevance.

Animals↗