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A Starzinski-Powitz

Publications and source records attributed to A Starzinski-Powitz.

46 records · Page 3Linked to original sources
PubMed1977

Cyclophosphamide-sensitive T lymphocytes suppress the in vivo generation of antigen-specific cytotoxic T lymphocytes.

Murine T lymphocytes sensitized in vitro against either allogeneic lymphocytes or syngeneic hapten-conjugated lymphocytes do differentiate into highly effective cytotoxic T lymphocytes (CTL) (1-3). In vivo immunization of T lymphocytes to the same antigens, however, results in the generation of only marginal cytotoxic activity (1,4,5). Recently we found that the weakness of in vivo generated cytotoxicity is not due to a failure of antigen-induced T-cell sensitization but rather due to suppression of the in vivo differentiation of sensitized CTL precursors into effective CTL(6). In keeping with this finding it was postulated that suppressor cells may regulate the in vivo differentiation of CTL. We now report, that cyclophosphamide-sensitive T cells suppress the in vivo differentiation of antigen-specific CTL. Thus, pretreatment of mice with a single dose of cyclophosphamide (100 mg/kg) converts their state of low responsiveness to a state of high responsiveness.

Animals↗
PubMed1977

Virion antigens introduced exogeneously into the cell membrane render syngeneic target cells susceptible for T cell-mediated cytolysis.

Non-infectious sendai virus renders H-2 matched target cells susceptible to the lytic effect of sendai virus immune cytotoxic T lymphocytes. This observation suggests that exogeneous insertion of virion antigen in the membrane of the target cell is sufficient for T cell cytotoxicity. The finding is incompatible with the concept that H-2K or H-2D gene products of the target cells must be altered in their primary structure (pretranslational effect of the virus infection) for T cell-mediated cytolysis to occur.

Animals↗
PubMed1977

Induction of I region-restricted hapten-specific cytotoxic T lymphocytes.

Murine cytotoxic T lymphocytes (CTL) reactive to TNP-conjugated syngeneic target cells do lyse to a moderate but significant extent TNP-conjugated, I region compatible but H-2K or H-2D region incompatible target cells. Antibody inhibition experiments and "cold inhibition" experiments indicate that some CTL clones recognize TNP-conjugated targets in association with syngeneic I region determinants independently of H-2K or H-2D gene products. The data suggest that besides TNP-conjugated H-2K or H-2D gene products, in principle, also TNP-conjugated I region determinants do stimulate TNP-specific CTL precursor cells and act as target antigens of TNP-specific CTL.

Animals↗
PubMed1977

The role of T cells in anti-herpes simplex virus immunity. I. Induction of antigen-specific cytotoxic T lymphocytes.

Mice infected with herpes simplex virus develop little or no cytotoxic T lymphocyte (CTL) response. However, in lymph nodes (LN's) draining a local site infected with HSV, antigen-specific CTL precursors are sensitized, which upon transfer to in vitro culture conditions develop within 72 hr into effective CTL. The in vivo blockade of CTL differentiation can be overcome by cyclophosphamide, suggesting that a cyclophosphamide-sensitive mechanism blocks the in vivo generation of HSV-immune CTL. The cytolytic activity of HSV-immune CTL is H-2 restricted and antigen specific. Thus CTL sensitized toward HSV type 1 discriminate between syngeneic targets infected with either the immunologic HSV variant type 1 or type 2 (and vice versa). H-2-matched target cells exposed for 30 min to infectious HSV are lysed within 60 min of contact with CTL. Since HSV replication is believed to require more than 4 to 5 hr, the data suggest that either the expression of HSV-dependent "early proteins" takes place within 30 to 90 min or cell membrane-integrated HSV virion represents the target antigen of CTL.

Animals↗
PubMed1976

Shared determinants between virus-infected and trinitrophenyl-conjugated H-2-identical target cells detected in cell-mediated lympholysis.

Infection of H-2-identical mice with either lymphocytic choriomeningitis (LCM) virus, vaccinia virus, or paramyxo (Sendai) virus resulted in the generation of specifically sensitized cytotoxic T lymphocytes (CTL). CTL generated in vitro against 2,4,6-trinitrophenyl (TNP)-conjugated syngeneic stimulator cells were specifically cytotoxic for TNP-conjugated H-2K (D) region identical targets. Both LCM and vaccinia-induced CTL, however, were found to be strongly cytotoxic towards TNP-conjugated, H-2K(D) region-identical target cells. In contrast, Sendai virus-induced CTL did not lyse TNP-conjugated, syngeneic target cells. Inhibition experiments using cold targets suggested that shared antigenic determinants can be detected on either LCM virus-infected and TNP-conjugated targets, which are not present on the cell surface of normal target cells.

Animals↗
PubMed1976

In vivo sensitization of T cells to hapten-conjugated syngeneic structures of major histocompatibility complex. I. Effect of in vitro culture upon generation of cytotoxic T lymphocytes.

Murine T cells were sensitized in vitro towards fluorescein isothiocyanate (FITC)-conjugated syngeneic spleen cells. The lytic activity of the effector cells generated was restricted to FITC-conjugated, H-2-compatible target cells. 2,4,6-Trinitrophenyl (TNP)-conjugated syngeneic targets were not lysed. A method is described for the in vivo sensitization of murine T cells towards TNP (or FITC)-conjugated syngeneic spleen cells. The procedure is based on the observation that a local graft of hapten-conjugated syngeneic spleen cells results in the development of sensitized prekiller T cells within the draining lymph node (LN). By mere in vitro incubation of such LN cells immunological specific anti-TNP (or anti-FITC)-reactive cytotoxic T lymphocytes (CTL) are generated. The in vitro differentiation of CTL requires 48-72 h; it is dependent on cell proliferation and is abolished by treatment of the LN cells with mitomycin C. Thus there is a separation between the sensitization of CTL precursors (which effectively takes place in vivo) and the phase of cell differentiation into CTL (which effectively takes place only in vitro). Similar to in vitro-sensitized CTL, the specificity of in vivo-sensitized CTL is dictated by the hapten used for the induction of the immune response and is restricted to hapten-conjugated syngeneic target cells.

Animals↗
PubMedDate not supplied

[Endometriosis--a stem cell disease?].

Endometriosis is an estrogen-dependent and chronic disease with an unknown etiology and pathogenesis. It is however likely and well accepted that retrograde menstruation of endometrial cells into the pelvic cavity is the origin of this disease in many cases. Here we discuss a model in which retrogradely menstruated endometrial cells have different inherent developmental properties because they represent in fact a mixture of different developmental cell stages. These stages can be distinguished in part by the expression of marker proteins such as cytokeratin (intermediate filament protein of epithelial cells) or E-cadherin (intercellular adhesion protein of epithelial cells and metastasis suppressor molecule). Cytokeratin-positive E-cadherin negative cells, for example, would be less differentiated epithelial cells than cytokeratin-positive E-cadherin positive cells. In analogy to findings in other cell systems we assume that the cells which are undifferentiated or not fully differentiated still have the potential to give rise to differentiated daughter cells and, on the other hand, could be maintained as a pool of rather undifferentiated cells and capable of self renewal. This feature would be similar to stem cells (SC) and cells with plasticity. Interestingly we find epithelial cells of different developmental stages in deep infiltrating (e. g. of colon) or peritoneal endometriotic lesions. Therefore we conclude that less differentiated cells in retrogradely menstruated endometrial cell populations possibly representing SC features or plasticity might be the cellular source of primary endometriotic lesions and those present in lesions may contribute to the persistence of the disease by detaching and forming secondary lesions.

Cell Differentiation↗
PubMedDate not supplied

Tracing cellular and molecular mechanisms involved in endometriosis.

The aetiology and pathogenesis of endometriosis, defined as the presence of endometrium-like tissue outside the uterine cavity, is largely unknown. In this paper we present and discuss possibilities to study the putative pathogenic properties of endometriotic cells in vitro. The current focus of our investigations is on the invasive phenotype of the disease, assuming that this might contribute to the pathogenesis of endometriosis. So far, we have shown that: (i) cytokeratin-positive and E-cadherin-negative endometriotic cells have an invasive phenotype in a collagen invasion assay in vitro similar to metastatic carcinoma cells; (ii) the invasiveness of endometriotic but not of eutopic endometrial cells can be stimulated by a heat-stable protein present in peritoneal fluid; and (iii) the endometriotic cell line EEC145T, which we established, may be a useful tool for the identification of gene products which are, positively or negatively, invasion-related. Finally, our studies suggest that the invasive phenotype in endometriosis shares aspects with tumour metastasis, but might also have unique mechanisms.

Ascitic Fluid↗