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Biomedical subjects

H Hirschberg

Publications and source records attributed to H Hirschberg.

At least 73 records · Page 4Linked to original sources
PubMed1981

Presentation of viral antigens by human vascular endothelial cells in vitro.

Endothelial cells (EC) separated from the umbilical vein were shown to be free of contaminating monocytes. EC could replace peripheral blood-derived macrophages as antigen-presenting cells for in vivo sensitized T cells towards a variety of viral antigens. The T-cell--CE-antigen response was also specificity inhibited by anti-HLA-DR antisera. T cells primed by antigen together with autologous macrophages could be restimulated by antigen pulsed HLA-D/DR identical EC in an antigen specific secondary response, indicating a similar mechanism for antigen presentation by EC or macrophages.

Antigens, Viral↗
PubMed1981

Vascular and renal distribution of HLA--DR-like antigens.

Tissue sections of ethanol-fixed, paraffin-embedded specimens from human kidney, placenta and umbilical cord were studied by indirect immunofluorescence with a rabbit antiserum to HLA--DR antigens from B lymphocytes. Capillary walls in the kidney showed specific staining both in glomeruli and around tubuli. Conversely, HLA--DR-like antigens were not detected in the walls of larger vessels, in tubular cells, or in the epithelium of Bowman's capsule. HLA-DR-like antigens of kidney elements thus seemed to be restricted to capillary endothelial cells. In specimens from umbilical cord and placenta, HLA--DR-like antigens were not detected in the walls of capillaries or larger vessels. Isolated endothelial cells from the umbilical vein were likewise negative.

Blood Vessels↗
PubMed1981

Antigen-presenting properties of human vascular endothelial cells: inhibition by anti-HLA-DR antisera.

Human vascular endothelial cells (EC) separated from the umbilical vein are capable of presenting antigen to in-vivo-sensitized T cells, leading to an immunoproliferative response to various antigens in vitro. Optimal T-cell response was only observed when the EC donor shared both HLA-D/DR determinants with the T-cell donor. The T-cell response normally observed when using antigen-pulsed EC was significantly and specifically inhibited by xeno- and allo-antisera reacting with the HLA-DR molecules. Moreover, antibodies reacting with the native antigen determinats (rubella virus) also appeared capable of inhibiting the response elicited by primed T cells to antigen-pulsed EC.

Animals↗
PubMed1980

Antigen-presenting properties of human vascular endothelial cells.

Human endothelial cells were obtained by collagenase digestion of the umbilical vein wall, explanted into tissue culture, and grown as monolayers of cells. Endothelial cells extracted from these monolayers were specifically lysed by anti-HLA-DR alloantisera. Moreover, the stimulating capacity of these endothelial cells toward allogeneic peripheral blood mononuclear lymphocytes was specifically and significantly inhibited by the presence of relevant anti-HLA-DR antisera. Endothelial cells that expressed HLA-DR determinants were also capable of substituting for macrophages in the lymphoproliferative response of purified T cells to soluble protein antigens. Moreover, in concordance with the results previously reported in which macrophages were employed, the endothelial cell donor should share HLA-DR determinants with the T cell donor for an optimal response to occur.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1980

Effects of methylprednisolone on the in vitro generation of human secondary cytotoxic lymphocytes.

The effects of methylprednisolone on the induction of secondary proliferative and cytotoxic lymphocytes in human mixed lymphocyte cultures (MLCs) have been studied. Concentrations of methylprednisolone (MP) as low as 0.01 microgram/ml proved highly effective in inhibiting the generation of cytotoxic memory cells if the steroid was present during the first 5 days of the priming mixed lymphocyte culture. The generation of cytotoxic lymphocytes was also inhibited if the steroid was added along with the restimulating cells on day 10, although the degree of inhibition was not as great as that seen when steroids were added to the cultures at their initiation. Cultures containing 1 microgram of MP per ml during the priming phase required 10 times as many effector cells to achieve a comparable level of cytotoxicity compared to control cultures without steroids. Our results indicate that an important aspect of the immunosuppressive role of steroids is the prevention of the generation of specific memory cells following exposure to alloantigens.

Cytotoxicity, Immunologic↗
PubMed1980

Effects of methylprednisolone on the in vitro induction and function of suppressor cells in man.

The effects of the steroid methylprednisolone on the induction of suppressor lymphocytes in human mixed lymphocyte cultures (MLC) have been examined. Concentrations of methylprednisolone (MP) sufficient to inhibit both the cellular proliferation and the generation of cytotoxic lymphocytes in MLC appeared to enhance the induction of suppressor cells in these cultures. Maximum enhancement of suppressor cell induction occurred at an MP concentration of approximately 1 microgram/ml. Moreover, the presence of low concentrations of methylprednisolone, not sufficient to inhibit proliferation in MLC, significantly potentiated the inhibiting effect of suppressor cells on cellular proliferation. The inhibition observed by the combined effect of MP and suppressor cells was equivalent to that seen using five times as many suppressor cells alone.

Cell Division↗
PubMed1980

Inhibition of blastogenic factor by alloantigen-activated human lymphocytes.

Human suppressor cells generated in mixed lymphocyte cultures (MLC) appear to inhibit both cellular proliferation and the mitogenic effects of blastogenic factor (BF). The results presented here indicate that the inhibition of BF by alloantigen-activated lymphocytes is not due to decreased lymphocyte proliferation as such, since BF normally produced by non-proliferating cultures was also suppressed. Moreover, the inhibition was not caused by direct suppression of the BF-producing lymphocytes, since incubation of BF with alloantigen-activated lymphocytes neutralized the mitogenic effects of BF. We therefore conclude that activated lymphocytes generated in human MLC directly inhibit or utilize BF. Our experiments also indicate that the activated lymphocytes do not have to proliferate to inhibit BF activity.

Cells, Cultured↗
PubMed1980

Opposing effects of methylprednisolone on in vitro alloantigen-induced cytotoxic and suppressor lymphocytes in man.

The effects of the steroid methylprednisolone (MP) on the induction of cytotoxic or suppressive lymphocytes in human mixed lymphocyte cultures (MLC) have been examined. Concentrations of MP sufficient to inhibit both the cellular proliferation and the generation of cytotoxic lymphocytes in MLC appeared to have very little effect on the induction of suppressor cells in these cultures. In fact, over a certain dosage range of MP an increased number of suppressor cells appeared to be generated. Moreover, low concentrations of MP greatly potentiated the effects of alloantigen induced suppressor cells but had little or no effect on the action of cytotoxic lymphocytes as measured in the cell mediated lympholysis assay. It seems therefore that MP has an opposing effect both on the generation and function of suppressor or cytotoxic lymphocytes induced by allogeneic cells.

Cell Division↗
PubMed1979

Clonal distribution of HLA-restricted antigen-reactive T cells in man.

The [3H]thymidine suicide technique was used to test the hypothesis that the response of immune human T cells from HLA-D/DR heterozygous donors to the soluble protein antigen purified protein derivative (PPD) is clonally expressed and consists of the concurrent proliferation of at least two separable subpopulations of lymphocytes. The results showed that each of the two subpopulations react to one or the other of the HLA-D/DR antigens presented together with PPD by allogeneic monocytes. In addition, using in vitro priming techniques of in vivo sensitized lymphocytes from heterozygous donors, it was possible to generate specific memory cells capable of recognizing the priming soluble protein antigen together with the HLA-D/DR determinant present in the initial sensitizing culture.

Cells, Cultured↗
PubMed1979

Specific destruction of human endothelial cell monolayers by anti-DRw antisera.

Human endothelial cells were separated by collagenase digestion from the umbilical vein of newborns. The cytotoxic effect of antisera against HLA-DRw antigens was tested on monolayers of endothelial cells, using a 51Cr retention microcytotoxicity assay in the presence of rabbit complement. Of the endothelial monolayers tested, significant concordance between the typing results obtained using cord blood-derived B lymphocytes and endothelial cell monolayers was observed. A rabbit anti-human polyspecific B cell antiserum was also capable of completely lysing the endothelial monolayers tested. In addition, 51Cr-labelled dissociated endothelial cells were lysed by nonimmune peripheral blood mononuclear cells in the presence of DRw antisera having a specificity for the target endothelium.

Antigens↗
PubMed1979

Cytotoxic effects of activated human monocytes and lymphocytes to anti-D-treated human erythrocytes in vitro.

Incubation of human monocytes, derived from peripheral blood, with cell-free supernatants from mixed lymphocyte cultures resulted in morphological and functional changes in the mature macrophages. Activation of monocyte-derived macrophages by these factors resulted in a significant increase in their capacity to lyse anti-D-treated human erythrocytes. The lytic activity of both normal and activated macrophages appeared to be independent of erythrophagocytosis. T lymphocytes activated by either allogeneic cells or the mitogen phytohaemagglutinin were not cytolytic to treated erythrocytes even at high effector to target cell ratios.

Antibodies↗
PubMed1978

In vitro immunosuppressive effects of cytotoxic agents conjugated to antihuman lymphocyte globulin.

Antihuman lymphocyte globulin (ALG) was either coupled to the lymphocytoxic drug chlorambucil or covalently bound to the cytotoxic alkalating agent melphalan via a polyglutamic acid carrier. Both types of complexes strongly inhibited the proliferative response in human mixed lymphocyte cultures and the ability of mixed lymphocyte culture-activated T effector cells to lyse 51Cr-labelled lymphoblast target cells, and were more potent than ALG or drug alone. These experiments indicate that it is possible to bind cytotoxic agents to ALG without destroying either the properties of the drug or the ability of the antibody to bind to lymphoid cells.

Antilymphocyte Serum↗