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T Hünig

Publications and source records attributed to T Hünig.

At least 91 records · Page 5Linked to original sources
PubMed1986

Kinetics of cellular oncogene expression in mouse lymphocytes. I. Expression of c-myc and c-ras-Ha in T lymphocytes induced by various mitogens.

Murine splenic T lymphocytes display maximal cellular myc gene (c-myc) expression already 3 h after concanavalin A stimulation and subsequent down-regulation before the onset of DNA synthesis. Stimulation by leucoagglutinin in the presence or absence of interleukin 2 leads to only low initial levels of c-myc-specific RNA which, however, increase later on. A similar pattern of c-myc expression is shown by the Lyt-2+ T cell subpopulation stimulated with either concanavalin A or leucoagglutinin in the presence of interleukin 2. Although [3H]thymidine incorporation was identical, the leucoagglutinin-stimulated Lyt-2+ T cells were void of any demonstrable c-myc-specific RNA at 3 h post-stimulation. Thus, the kinetics of c-myc expression in mouse T lymphocytes are not at all uniform, but depend on the mitogen and the subpopulation. In contrast, levels of c-ras-Ha-specific RNA were always low at early times, always increased towards the onset of DNA synthesis and down-regulation was not observed.

Agglutinins↗
PubMed1986

T11TS, the cell surface molecule binding to the "erythrocyte receptor" of T lymphocytes: cellular distribution, purification to homogeneity and biochemical properties.

T11 target structure (T11TS) is a sheep cell surface glycoprotein that binds to the E receptor of human and sheep T lymphocytes. Here we report that T11TS has a broad tissue distribution, including mature and immature hematopoietic cells, vascular endothelium and smooth muscle. The density of T11TS expression was determined by Scatchard analysis with radiolabeled anti-T11TS monoclonal antibody. Red blood cells bound 10,000, and leukocytes bound 4000 to 23,000 antibody molecules per cell. T11TS was purified to homogeneity by immune-affinity and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and some of its biochemical properties were determined. T11TS is an acidic (pI 4.5) membrane glycoprotein that binds to concanavalin A. It has 2 or 3 N-glycosidically linked carbohydrate side chains of the mature phenotype, no O-linked sugars, and an apparent mol. mass of 42 kDa (glycosylated) and 32 kDa (deglycosylated). The anti-T11TS monoclonal antibody L180/1, which blocks binding of sheep red blood cells to CD2, recognizes a protein determinant on T11TS. These findings are discussed with respect to the possible function of the CD2-T11TS system as a set of complementary cell interaction molecules involved in T cell activation.

Antibodies, Monoclonal↗
PubMed1985

The cell surface molecule recognized by the erythrocyte receptor of T lymphocytes. Identification and partial characterization using a monoclonal antibody.

A monoclonal antibody (mAb) to sheep red blood cells (SRBC), termed L180/1, is described that completely blocks rosette formation between SRBC and human or sheep T lymphocytes. L180/1 precipitated a minor glycoprotein of about approximately 42,000 mol wt from surface-labeled SRBC. This glycoprotein was partially affinity purified and found to block E rosette formation and to compete with anti-T11 mAb for the E receptor. The molecule detected by mAb L180/1 thus appears to be recognized by the E receptor and was given the preliminary name, T11 target structure (T11TS). Since the mAb to sheep T11TS blocks the binding of SRBC to both human and sheep T cells, and mAb to T11 blocks the binding of red cells from human and sheep to the human E receptor, we concluded that analogous receptor-ligand (T11-T11TS) systems exist in man and sheep that are crossreactive over the species barrier. The possibility is discussed that the E receptor, which is known to be involved in T cell activation, and T11TS function as complementary cell interaction molecules in T cell responses.

Animals↗
PubMed1985

Induction of proliferative and cytotoxic responses in resting Lyt-2+ T cells with lectin and recombinant interleukin 2.

The 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 concanavalin 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-2+ T cells.

Animals↗
PubMed1985

Analysis of the negative allogeneic effect using B cells and helper T cell lines as an indicator system: B cells identified as target cells for suppression.

The target cells for H-2b T lymphocytes mediating a negative allogeneic effect in vitro were analyzed by using carrier-specific helper T cell lines of H-2b, H-2d, or F1 origin and hapten-primed T-depleted spleen cells also expressing one or both of these haplotypes. The helper T cell lines were shown to be carrier specific and H-2b or H-2d restricted. Most importantly, the lines derived from H-2b homozygous mice were devoid of alloreactivity against H-2d and vice versa. Titration of naive H-2b T lymphocytes to the indicator cultures resulted in suppression of the secondary anti-DNP response of the indicator cells whenever the B cells expressed H-2d antigens. The lack of suppression observed in mixtures in which only the helper T cell lines expressed H-2d antigens was not reversed by the increased addition of naive H-2bxd cells, indicating that an insufficient amount of H-2d antigens present on the low number of helper T cells used did not account for this finding. Moreover, the polyclonal plaque-forming cell responses of F1 spleen cells to LPS were also suppressed by naive parental T cells. From these findings it is concluded that the suppressor T cells directly recognize and inhibit allogeneic B cells without the involvement of helper T cells. In addition, it was shown that the suppression of secondary anti-hapten responses by naive allogeneic T cells is blocked by monoclonal anti-Lyt-2 antibody added at the onset of culture. Addition late in culture had no effect, pointing to a functional role of the Lyt-2-bearing structure at an early stage of the suppressive events resulting in the negative allogeneic effect.

Animals↗
PubMed1984

Monoclonal anti-Lyt-2.2 antibody blocks lectin-dependent cellular cytotoxicity of H-2-negative target cells.

The hypothesis that blocking of cytotoxic T lymphocyte (CTL)-mediated cytolysis with anti-Lyt-2 antibodies acts at the level of inhibiting the interaction of the Lyt-2-bearing structure with H-2 class I molecules was tested. In agreement with the findings of others, purified anti-Lyt-2.2 inhibited both antigen-specific lysis and lectin-dependent cellular cytotoxicity (LDCC). LDCC of H-2-positive and H-2-negative target cells was similarly inhibited by this antibody. As expected, this effect was specific for CTL expressing the Lyt-2.2 allele, in contrast to blocking with a rat monoclonal antibody to the murine LFA-1 antigen. The implications of this finding for the function of the Lyt-2 antigen in CTL-target cell interaction are discussed.

Animals↗
PubMed1984

The role of accessory cells in polyclonal T cell activation. III. No requirement for recognition of H-2-encoded antigens on accessory cells.

Highly purified murine lymph node T cells were used to test the hypothesis that polyclonal T cell activation requires the recognition of mitogen-modified major histocompatibility complex (MHC) antigens on accessory cells (AC) by the T cells. A variety of tumor cells lines, including macrophage, B and mast cell tumors, as well as thymomas, were shown to function as AC in concanavalin A-induced T cell activation, even if they expressed only one class of MHC antigens or none at all. In contrast to antigen-specific responses, where the Lyt-2+ phenotype is reportedly associated with recognition of class I MHC antigens, T cells enriched for or depleted of Lyt-2+ cells were not preferentially activated in the presence of class I- or class II-positive AC, respectively. In addition, as shown by others in the guinea pig and in the rat systems, T cell proliferation induced by oxidation of cell surface sugars is equally effective if T cells or AC are oxidized. T cell mitogens, therefore, do not seem to act by altering MHC antigens on AC, but rather by providing T cell-AC contact via their agglutinating properties.

Animals↗
PubMed1983

The role of accessory cells in polyclonal T cell activation. I. Both induction of interleukin 2 production and of interleukin 2 responsiveness by concanavalin A are accessory cell dependent.

Recent studies from other laboratories have shown that concanavalin A (Con A) acts at two separate steps in polyclonal T cell activation: interleukin 2 (IL2) production, and induction of responsiveness to IL2. Using a combination of techniques for the depletion of accessory cells from lymph node T cells, we have investigated which of these steps, if not both, is responsible for the known requirement for accessory cells in the Con A response. It was found that with increasing T cell purification, first the ability is lost to produce sufficient levels of endogenous IL2, whereas induction of IL2 responsiveness can still take place. Further removal of accessory cells however yields a population of resting T cells that cannot be induced by Con A to become IL2-reactive. It was concluded that both IL2 production and induction of reactivity to IL2 are accessory cell-dependent events.

Animals↗
PubMed1983

The role of accessory cells in polyclonal T cell activation II. Induction of interleukin 2 responsiveness requires cell-cell contact.

It has previously been reported (Hünig, T. et al., Eur. J. Immunol. 1983. 13:1) that highly purified peripheral T cells do not respond to concanavalin A (Con A) even in the presence of Con A-induced spleen cell supernatant as a source of interleukin 2 (IL 2). In the present report, the hypothesis was tested whether this unresponsiveness correlates with the observed inability of Con A to mediate cell-cell contact between highly purified T cells. It was found that T cells, pretreated with neuraminidase to reduce their net negative charge, were both aggregated and rendered IL 2-reactive by Con A. In addition, leukoagglutinin (LA) was found to be able to both agglutinate untreated T cells and to make them IL 2-reactive. Neuraminidase treatment reduced the concentration of LA required to mediate both effects. Neuraminidase treatment did not alter the overall Con A-binding capacity of T cells, nor did it induce reactivity to IL 2 in the absence of lectin. Furthermore, irradiated, neuraminidase-treated T cells served as accessory cells (AC) in the induction of responsiveness to IL 2, but not for production of IL2, which depends on Ia+ AC. Finally, Lyt-2- neuraminidase-treated peripheral T cells responded in the same fashion as whole T cell populations, indicating that at least some T cells of the helper phenotype need not interact with Ia+AC for the induction of IL 2 responsiveness.

Animals↗
PubMed1982

T cells produce TRF in response to Con A and factors in T cell hybridoma supernatants.

In recent experiments, a soluble factor (TRF) that mediates the differentiation of anti-immunoglobulin (Ig)-activated B cells to Ig-secreting cells has been identified. TRF works in concert with a growth factor, probably IL 2, in the induction of activated B cells. In previous studies, TRF was identified in culture supernatants of activated T cells and accessory cells, and thus the cellular source (T cell or accessory cell) of the factor was not determined. In the present studies, we succeeded in inducing the production of TRF by T cell populations from which accessory cells had been vigorously depleted. Lymph node cells were depleted of accessory cells by nylon wool adherence and anti-Ia and complement treatment; these cells were activated with Con A and a T cell hybridoma supernatant that contains IL 2. Supernatants from these activated T cell cultures supported the differentiation of anti-Ig-activated B cells to Ig secreting cells. These results show that T cells produce the differentiation factor, and further that they do so in response to ligand (Con A) plus a T cell-derived factor.

Animals↗
PubMed1981

T cells respond preferentially to antigens that are similar to self H-2.

We have constructed bone marrow irradiation chimeras to investigate the influence of self antigens on the specificity of the T lymphocyte receptor repertoire. Bone marrow cells from (A X B)F1 mice heterozygous for the major histocompatibility genes were allowed to mature into T cells in irradiated parent A or parent B strains. More than 8 weeks after irradiation, when the lymphoid system had regenerated from the F1 stem cells, the degree of T cell reactivity to mutant major histocompatibility antigens, A', was assessed. It was found that T cells that had matured in the irradiated A mice, [F1 leads to A] chimeras, responded better to A' antigen than did T cells from the [F1 leads to B] chimeras. Because the mutant histocompatibility antigen A' is very similar in structure to A, differing only by one or a few residues, this suggests that the T cell repertoire in [F1 leads to parent] chimeras reacts preferentially with foreign antigens that are slight variants of the self antigens expressed on radiation-resistant cells--probably cells in the thymus.

Animals↗
PubMed1980

Specificity of cytotoxic T cells from athymic mice.

In normal mice, self-H-2 antigens in the thymus have a profound influence on T cell specificity. We have therefore investigated the properties of cytotoxic T lymphocyte (CTL) precursors from athymic nude mice (5) with the notion that they may provide a model system for the study of T cells whose receptro specificity is closer to the germ-line-encoded repertoire. It was found that the precursors of nude CTL are, themselves, THy-1+ cells. The possibility that these nude t cells were derived from the phenotypically normal mother by placental transfer was ruled out. In the presence of T cell growth factor, nude CTL can be induced by polyclonal activation with concanavalin A or by stimulation with allogeneic or trinitrophenyl (TNP)-modified syngeneic stimulator cells, but not by stimulation with minor H antigens in the context of self-H-2. Alloreactive, nude CTL--like those from normal mice--recognize H-2K- and H-2D-region-encoded antigens in killer-target cell interactions, but, unlike normal CTL, did not cross-react on third-party target cells. Whereas the anti-TNP response of nude mice is H-2 restricted, it does not seem to be influenced by self-H-2 antigens in the same manner as in normal mice. This is suggested by the finding that the immunodominance of H-2k over H-2d in the anti-TNP-self response of normal (H-2d X H-2b)F1 mice is absent in (H-2d X H-2k)F1 nude mice. These observations are discussed in relation to the role of the thymus in the generation of the normal mature T cell receptor repertoire.

Animals↗
PubMed1980

Self H-2 antigens influence the specificity of alloreactive cells.

We have tested Jerne's hypothesis (9) that the phenomenon alloreactivity is explained by the existence of T cells that express germline-encoded receptors specific for major histocompatibility complex antigens and that these cells undergo no change in specificity during thymic differentiation. T cells from [F1 leads to Parent] bone marrow radiation chimeras reactive to conventional antigens are known to have a self preference, i.e., [A X B leads to A] chimeras respond better to H-2A-plus-antigen than to H-2B-plus-antigen. We show here that alloreactive cells from such chimeras also have a self preference. Thus, H-2k-specific alloreactive T cells from [H-2b X H-2d leads to H-2b] and [H-2b X H-2d leads to H-2d] chimeras cross-react more on TNP-modified H-2b or H-2d targets, respectively. In contrast to Jerne's prediction, the results suggest that the receptor repertoire of alloreactive F1 cells is influenced by H-2 antigens on radiation-resistant cells present during T cell ontogeny. By this criterion of having a self preference in H-2 restriction, alloreactive T cells appear to be similar to T cells that respond to conventional antigens.

Animals↗
PubMed1979

Studies on the generation and expression of H-2-controlled T helper function in chimeric mice: evidence for two levels of H-2 resitriction.

F1 leads to parental, semisyngeneic/semiallogeneic and fully allogeneic bone marrow radiation chimeras were used as a source of helper T cells in the in vitro anamnestic response to dinitrophenylated keyhole limpet hemocyanin. In F1 leads to parental and in semisyngeneic/semiallogeneic chimeras, a small population of helper T cells restricted to the H-2 haplotype present in the donor only was shown to co-exist with T cells restricted to the shared haplotype. Only the population restricted to the donor H-2 could be demonstrated in allochimeras, presumably due to a lack of antigen-presenting cells of host origin during priming. Under assay conditions where, in addition to T cell/macrophage interactions, a direct T-B cell contact was necessary ("linked" cooperation), the H-2 restrictions observed were absolute. When direct T-B cell contact was made unnecessary by a special experimental protocol ("unlinked" cooperation), H-2 restriction between T and B cells was overcome. Thus, the cellular interactions during the anamnestic immune response to T-dependent antigens seem to be H-2-restricted at two levels: T cell/macrophage and T-B cell interactions.

Animals↗