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E Kölsch

Publications and source records attributed to E Kölsch.

At least 55 records · Page 3Linked to original sources

Selective in-vitro activation of BALB/c T suppressor lymphocytes specific for syngeneic ADJ-PC-5 plasmacytoma cells.

T suppressor (Ts) lymphocyte activation is the first reaction of the immune system under conditions which simulate early stages of tumourigenesis. There is evidence that the Ts cell inducing antigen on ADJ-PC-5 plasmacytoma cells of BALB/c origin is a self antigen, which is also expressed on normal BALB/c spleen cells. In order to study this Ts cell inducing determinant in more detail we have developed an in vitro system which allows the selective activation of ADJ-PC-5 specific Ts cells in the absence of activation of cytotoxic T (Tc) cells. The system now allows us to study the modulation of Ts cell induction and function.

Animals↗

An evaluation of the existence of soluble suppressor factors in cloned antigen-specific T suppressor lymphocytes.

The suppressive activity of two bovine serum albumin-specific class II-restricted T suppressor cell clones (BVI/5 and 83/2-D11) was compared to that of a feeder cell-independent, IL 2-dependent subline (HF1.IL-2) of an originally antigen-dependent class II-restricted Ts cell clone (HF1). No soluble suppressor factors can be found in BVI/5 and 83/2-D11 Ts cell extracts or culture supernatants under conditions where an unspecific factor can be derived from HF1.IL-2 cells. This factor, when isolated from cell extracts in the presence of n-octyl-beta-D-glycopyranoside, has a molecular weight of 70-80 kD. In absence of this non-ionic detergent, it has a high affinity to membrane fragments and is associated with a molecular weight of 300 kD or more. The data are discussed in connection with recent findings of direct T suppressor to T helper interaction by cell-cell contact.

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Isolation of a bovine serum albumin-specific T-suppressor cell clone and evaluation of its in vitro functions.

This communication describes a newly isolated T-suppressor (Ts) cell clone, BVI/5, derived from a CBA/J mouse tolerized to low doses of bovine serum albumin (BSA). The cells are Thy-1.2+, Lyt-1.1-, Lyt-2.1+, and express endogenous derived I-Ak and I-Ek molecules. BVI/5 Ts cells show antigen-specific I-Ek-restricted proliferation in the presence of antigen-presenting spleen cells. This proliferation can be inhibited by anti-I-Ek but not by anti-I-Ak monoclonal antibodies. In vitro antigen-specific suppressive capacity has been measured in a primed lymph node cell proliferation assay, and the fine specificity of these suppressor functions has been studied. Broader cross-reactivity in the specificity of this effector function is found if compared to the specificity of antigen-induced proliferation. The data extend previous findings on the expression of I-A and I-E molecules on Ts cells and are discussed with respect to the role of those cells in tolerance induction.

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Selective elimination through a cytolytic mechanism of bovine serum albumin-specific T helper lymphocytes by T suppressor cells with the same antigen specificity.

An antigen-specific T suppressor cell clone isolated from a CBA/J mouse tolerized to low doses of bovine serum albumin (BSA) has previously been analyzed with regard to its effector functions. The T suppressor cell clone HF1 specifically inhibits T helper cell responses to the antigen. It also has characteristic cytolytic activity which can neither be classified as cytotoxic T cell nor as natural killer cell activity. Since this lytic capacity might be of relevance in immunoregulation, it has now been studied in more detail. For that purpose BSA-specific T cell lines have been isolated from immune CBA/J mice in order to test them in 51Cr-release assays as possible targets for HF1 T suppressor cells. Two T cell lines, both BSA specific and restricted to recognition of I-Ek major histocompatibility complex determinants, have been selected for the studies because one is a helper cell (83/1), the other a suppressor cell type (83/2). HF1 T cells are able to lyse cells of line 83/1 but not those of line 83/2. Control experiments show that 83/1 cells are not a natural killer cell target and that on the other hand 83/2 cells are susceptible to lysis in an alloreactive BALB/c anti-CBA/J cytotoxic T cell response. The extent of lysis of 83/1 T cells by HF1 T cells changes with time after antigenic stimulation. The lysis is based on direct effector: target cell interaction and not caused by soluble mediators. The data are discussed with regard to the effector function of a type of T suppressor cells which expresses I-A and I-E molecules and whose proliferation is restricted to the recognition of I-A or I-E determinants.

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Evidence for a T suppressor cell-inducing antigenic determinant shared by ADJ-PC-5 plasmacytoma and syngeneic BALB/c spleen cells.

The BALB/c plasmacytoma ADJ-PC-5 induces in early stages of tumorigenesis specific T suppressor (Ts) cells apparently as the first reaction of the immune system towards the growing tumor. In attempts to apply the concept of early induction of Ts cells in neoplasia for the induction of tolerance to allografts we have tried to induce Ts cells against alloantigens by injecting allogeneic spleen cells in doses increasing exponentially from 10 to 10(5) cells/mouse. Experiments using various strain combinations failed to demonstrate induction of specific Ts cells by this procedure. To explain the apparent discrepancy between these and the tumor data the capacity of the ADJ-PC-5 tumor cells to induce Ts cells in allogeneic combinations was analyzed. ADJ-PC-5 cells are capable of inducing specific Ts cells in CBA/J mice. These Ts cells specifically suppress the induction of a primary cytotoxic T cell response of CBA/J spleen cells against BALB/c, BALB.B and (BALB/c X C57BL/6)F1 cells but not one against B10.D2 or C57BL/10 target cells. The ADJ-PC-5-induced CBA/J Ts cells have been further analyzed using a panel of different target or responder cells. From these experiments the following conclusions can be drawn: the CBA/J Ts cells are specific for an antigen which is shared by ADJ-PC-5 and normal BALB/c spleen cells. The antigen in question is not coded for by the H-2d major histocompatibility complex. The data suggest that the Ts cell-inducing antigen on ADJ-PC-5 tumor cells is not a tumor associated neoantigen but a self antigen also present on normal BALB/c lymphoid cells.

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Expression of L3T4 molecules on Lyt-2+, class II-restricted antigen-specific T suppressor lymphocytes.

Three bovine serum albumin-specific Lyt-2+ T suppressor (Ts) cell clones from CBA/J mice have been analyzed with regard to expression of L3T4 molecules. All three Ts-cell clones can be stained with monoclonal antibodies (mAb) to L3T4. Tested for the two clones restricted to recognition of Ek determinants, antigen-specific proliferation on antigen-presenting cells, but not the proliferation induced by conditioned medium can be inhibited by L3T4-specific mAb. In a similar way, Ts-cell cytolytic effector functions can be blocked by L3T4-specific mAb. Thus L3T4 structures seem to play a role in Ts-cell functions. Furthermore, the data support the view that L3T4 expression can be a property of class II-restricted T cells irrespective of their Lyt phenotype.

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Regulation of immune responses against the syngeneic ADJ-PC-5 plasmacytoma in BALB/c mice. IV. Tumor-specific T suppressor cells, induced at early stages of tumorigenesis, act on the induction phase of the tumor-specific cytotoxic T cell response.

The BALB/c plasmacytoma ADJ-PC-5 induces specific non-cytolytic T suppressor (Ts) cells under experimental conditions which closely resemble early stages of tumorigenesis. The phenotype of these Ts cells is Thy-1.2+, Lyt-1.2-, Lyt-2.2+, I-Ad-. They inhibit the induction of the cytotoxic T cells in a primary mixed lymphocyte tumor culture (MLTC) against the ADJ-PC-5 plasmacytoma. Specificity of suppression can be demonstrated by testing them in MLTC against a panel of syngeneic control tumor. Only the induction phase of a primary MLTC can be suppressed, and within 24 h of MLTC, cytotoxic T (Tc) cells become resistant towards suppression. ADJ-PC-5-specific Tc cell clones are also resistant to suppression. The fact that Ts cell-mediated specific suppression can be overcome by addition of semipurified IL2 to the MLTC suggests that Th cells, and not Tc cell precursors, are the target. The findings are discussed with respect to the potential use of Tc effector cells in cancer therapy.

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Isolation and characterization of in vitro and in vivo functions of a tumor-specific T suppressor cell clone from a BALB/c mouse bearing the syngeneic ADJ-PC-5 plasmacytoma.

A spontaneously transformed T suppressor (Ts) clone, A12-D11/t, is described which arose from the antigen-specific Ts clone A12-D11 isolated from cells of the inguinal lymph node of a BALB/c mouse bearing the syngeneic plasmacytoma ADJ-PC-5. A12-D11/t Ts cells suppress in vitro specifically a primary syngeneic cytotoxic antitumor response with the consequence that no ADJ-PC-5-specific cytotoxic T cells can be generated. The in vivo effects of A12-D11/t Ts cells were studied by injecting them into BALB/c mice. Spleen cells from those mice subsequently failed to respond against ADJ-PC-5 plasmacytoma cells, whereas their response against other syngeneic BALB/c tumors remained unaffected. By using a model system which allows us to study the host's immune reactions to the antigenic load corresponding to initial stages of tumorigenesis, it has been shown previously that ADJ-PC-5-specific Ts cells are activated before the antigen threshold for the activation of cytotoxic T cells is reached. Regarding its phenotype and specificity, the A12-D11/t Ts clone seems to be the exact counterpart of such a Ts cell, and is therefore of special interest in the study of the role of Ts cells preventing immunity against a growing tumor.

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Functional studies on the role of I-A molecules expressed by the antigen-specific T suppressor cell clone HF1.

The antigen-specific T suppressor (Ts) cell clone HF1 (Thy-1.2+, I-Ak+, I-Ek+) was isolated from a CBA/J mouse tolerized to low doses of bovine serum albumin (BSA), and a subclone was adapted to grow in the absence of antigen-presenting cells. The functional role of the I-Ak molecules endogenously expressed by HF1 Ts cells was analyzed by using anti-I-Ak monoclonal antibodies (mAb) in attempts to block the antigen-induced proliferation of these cells. Among a panel of anti-I-Ak mAb tested, only the H118-49 mAb directed against the private determinant Ia.m1 blocked BSA-induced proliferation. The data presented here suggest a selective regulatory role of membrane-bound I-Ak molecules in the antigen-induced signal transmission.

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Natural killer cell-mediated cytotoxicity does not depend on recognition of mannose 6-phosphate residues.

Interaction of mannose 6-phosphate-specific receptors with their ligands has been suggested to be essential for natural killer cell (NK)-mediated cytotoxicity. Indeed, mannose 6-phosphate-specific receptors and ligands bearing mannose 6-phosphate residues are demonstrable on human peripheral blood leukocytes with NK activity as well as on K-562 NK target cells, allowing at least in principle such an interaction. It can also be shown that NK activity of human peripheral blood leukocytes is inhibited by mannose 6-phosphate. The following observations, however, exclude an essential role of the mannose 6-phosphate receptor-ligand system in NK cell-mediated cytotoxicity. 1) NK cytotoxicity is sensitive to a broad range of structurally unrelated sugar phosphates. 2) NK activity is normal in patients with I cell disease (mucolipidosis II), which due to a genetic defect are unable to synthesize the ligands for the mannose 6-phosphate-specific receptor. 3) NK cytotoxicity is not inhibited by an antiserum against the mannose 6-phosphate receptor, which blocks the receptor function.

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Immune response against the T-independent antigen alpha (1----3) dextran. II. Occurrence of B gamma memory cells in the course of immunization with the native polysaccharide is T cell dependent.

The immune response of BALB/c mice against the bacterial antigen dextran B1355S [alpha (1----3)dextran] (Dex), a class 2 T cell-independent antigen, is largely restricted to IgM class antibody production. However, despite the fact that Dex fails to give rise to enhanced IgG responses upon repeated immunization, the development of Dex-specific B gamma memory cells, i.e. resting B cells committed to the production of specific IgG antibodies, is observed upon immunization with Dex. These B gamma memory cells, albeit not activated to IgG production in situ, can be activated upon adoptive transfer into irradiated congenic BALB Ighb mice. This mouse strain is a nonresponder strain to Dex. The expression of adoptively transferred Dex-specific B gamma memory cells is T cell-independent as T cell depletion of spleen prior to cell transfer into BALB.Ighb recipients does not abolish the IgG response. Dex-primed athymic BALB/c nude mice, in contrast to euthymic mice, give a pronounced primary IgG response but do not develop Dex-specific B gamma memory cells. Yet, they do so when reconstituted with syngenic T cells prior to immunization. This indicates that the formation of Dex-specific B gamma memory cells requires the presence of functional T cells. The pronounced primary IgG anti-Dex response of nude mice is greatly impaired by T cell reconstitution. Thus, with regard to T cell dependence, there is an inverse relationship between the formation of B gamma memory cells and the capacity to produce IgG anti-Dex. Dex-specific B gamma memory cells from BALB/c mice are expressed in congenic BALB.Ighb recipients (nonresponder to Dex) but not when transferred into identically treated syngenic hosts. This also applies to memory cells from Dex-primed female (CBA/N X BALB/c)F1 [NBF1] or from (BALB/c X CBA/N)F1 hybrids. Dex-specific B gamma memory cells from these donors are demonstrable upon adoptive transfer into BALB.Ighb mice, but they are not expressed when transferred into syngenic recipients, including male NBF1 hybrids. NBF1 males, albeit possessing the VH-Dex+ allele, do not mount humoral responses to Dex, a deficiency which is ascribed to an X chromosome-linked B cell defect. The apparent absence of Dex-specific antibodies in NBF1 males provides an opportunity to examine whether B gamma memory cell expression is inhibited in syngenic recipients by anti-Dex or autologous anti-idiotype antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

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Modulation of the antigraft response by preimmunization. Lack of correlation between regulatory events and graft survival.

Using two H-2 congeneic mouse strain combinations, the effect of donor specific i.v. preimmunizations with allogeneic spleen cells was studied. Parameters analyzed were survival time of the subsequent skin graft, graft-induced delayed-type hypersensitivity (DTH) reactions, and humoral immune responses evoked by immunization and grafting. Depending on the dose of allogeneic cells used for preimmunization, a suppression of the DTH response was observed, commonly accompanied by a similarly dose-dependent antibody formation that was inversely related to the DTH response. Neither DTH reactivity nor the antibody response were correlated in this system with the survival time of the skin graft. The only modulation of the survival time to be observed was an accelerated rejection of the graft caused by nonirradiated, as compared with irradiated, donor spleen cells. The data are discussed with regard to the clinically observed effect of blood transfusions on the survival of renal transplants and the relationship between DTH and graft rejection.

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Analysis of the growth characteristics of a primary BALB/c IgG plasmacytoma.

Spontaneously arising and chemically or virally induced tumors usually cannot be analyzed in the early stages of tumorigenesis. Growth characteristics of these tumors thus are not available and it is unknown whether their expansion at any stage is influenced by the immune system. We have developed the following strategy to evaluate possible deviations from exponential growth in initial stages when a tumor is not yet manifest and in order to overcome the two main objections against most experiments in tumor immunology: use of possibly selected transplantable tumors and high initial cell doses. BALB/c mice received 0.5 ml of Pristane intraperitoneally three times within 16 weeks. This treatment induces plasmacytomas in 58% of the animals within 1 year. Mice were bled twice a week beginning with the 5th week after the last injection and sera were stored. Guinea-pig anti-idiotypic antibodies were raised against the IgG myeloma protein of a plasmacytoma developing in mouse 6-15 and a radioimmunoassay was set up. Sera of mouse 6-15 were then tested in retrospect for appearance and increase of the myeloma idiotype Id 6-15. We followed this idiotype thus for 19 weeks from a concentration of about 10 micrograms/ml up to 3 mg/ml serum. Plasmacytoma 6-15 cell growth was calculated from the Id 6-15 levels. In early phases wave-like fluctuations were found, possibly due to varying ratios of secretor to total plasmacytoma 6-15 cells. This phase was followed by an exponential increase in secretor cell number. At no time was there evidence for anti-idiotypic auto-antibodies against Id 6-15. The data are discussed in connection with possibly early activation of cellular components of the immune system.

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Neutral glycosphingolipids of murine myeloma cells and helper, cytolytic, and suppressor T lymphocytes.

Functionally defined clones and lines of murine lymphocytes including myelomas, helper, suppressor and cytolytic T lymphocytes were analyzed for their glycosphingolipids (GSLs). GSLs were characterized by thin-layer chromatography and by high-performance liquid chromatography. Lymphocytes with different functions displayed, besides a number of common GSLs, some characteristic GSLs that may be regarded as markers. Globotriaosylceramide was found on myelomas and B blasts, whereas globotetraosylceramide was confined to helper T cells. All T cells including cytolytic T lymphocytes displayed gangliotetraosylceramide (asialo-GM1) as a major GSL, which was further characterized by sequential degradation with exoglycosidases.

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