scholarly journals STUDIES ON CELL-MEDIATED IMMUNITY TO LYMPHOCYTIC CHORIOMENINGITIS VIRUS IN MICE

1973 ◽  
Vol 137 (6) ◽  
pp. 1511-1525 ◽  
Author(s):  
Ole Marker ◽  
Mogens Volkert
Keyword(s):  
Time Course ◽  
Underlying Mechanism ◽  
Cell Interaction ◽  
Lymphocytic Choriomeningitis ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Cell Mediated Immunity ◽  
Sharp Maximum ◽  
Direct Cell

A large amount of experimental evidence has already been presented indicating the great importance of the cell-mediated immunity in the pathogenesis of the LCM virus infection in mice. In this laboratory a method which makes it possible to measure this cellular immunity quantitatively in vitro has been developed. The method is based on the determination of the radioisotope released after the interaction between specifically sensitized lymphocytes and syngeneic 1Cr-labeled LCM virus-infected target cells. By using this technique the time-course of the cell-mediated immunity has been established in acutely infected mice and in virus carriers adoptively immunized with syngeneic sensitized lymphocytes. Lymphocytes from acutely infected mice showed a strong lysing effect on the target cells, with a sharp maximum at about the 9th day after infection. The cell-mediated immunity in adoptively immunized virus carrier mice showed the same time-course, but in these animals the lytic effect of the lymphoid cells was considerably less pronounced. Lymphocytes from untreated virus carriers did not, however, have any effect on the target cells, and in these animals it was not possible to demonstrate any evidence of enhancing antibodies, In experiments employing serial dilutions of sensitized lymphocytes in normal cells a direct linear relationship between the number of sensitized lymphocytes and target cell destruction was found. These experiments seem to indicate that the underlying mechanism in the cytotoxic reaction is a direct cell-to-cell interaction.

scholarly journals CELL-MEDIATED CYTOTOXICITY DURING REJECTION AND ENHANCEMENT OF ALLOGENEIC SKIN GRAFTS IN RATS

1972 ◽  
Vol 135 (6) ◽  
pp. 1301-1315 ◽  
Author(s):  
Hans-Hartmut Peter ◽  
Joseph D. Feldman
Keyword(s):  
Lymph Nodes ◽  
Thoracic Duct ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Skin Grafts ◽  
Peak Activity ◽  
Adult Rats ◽  
Background Levels

Cell-mediated cytotoxicity (CMC) in spleens and lymph nodes of allografted rats was determined by release of 51Cr from labeled target cells incubated with aggressor lymphoid cells. CMC was first detected in grafted adult rats on day 5, peaked on days 7 and 8, and declined rapidly to background levels by days 9 to 11. In allografted neonates and in cyclophosphamide-treated or neonatally thymectomized adults CMC was a fraction of that observed in normal adult rats. Enhancing antibodies deferred in vivo peak activity of CMC in allografted neonates for 3–4 days, and blocked in vitro the action of aggressor lymphocytes by binding to target cells. Enhancing antibodies had no effect on the cytotoxicity of aggressor cells, but horse antibodies to rat thoracic duct cells inhibited in vitro CMC of aggressor cells.

scholarly journals CD18 Antibody Application Blocks Unwanted Off-Target T Cell Activation Caused by Bispecific Antibodies

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4596
Author(s):  
Joseph Kauer ◽  
Fabian Vogt ◽  
Ilona Hagelstein ◽  
Sebastian Hörner ◽  
Melanie Märklin ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphoid Cells ◽  
Bispecific Antibodies ◽  
Target Cells ◽  
Cytokine Release ◽  
Life Threatening ◽  
Blocking Antibodies

T cell-recruiting bispecific antibodies (bsAbs) are successfully used for the treatment of cancer. However, effective treatment with bsAbs is so far hampered by severe side effects, i.e., potentially life-threatening cytokine release syndrome. Off-target T cell activation due to binding of bispecific CD3 antibodies to T cells in the absence of target cells may contribute to excessive cytokine release. We report here, in an in vitro setting, that off-target T cell activation is induced by bsAbs with high CD3 binding affinity and increased by endothelial- or lymphoid cells that act as stimulating bystander cells. Blocking antibodies directed against the adhesion molecules CD18/CD54 or CD2/CD58 markedly reduced this type of off-target T cell activation. CD18 blockade—in contrast to CD2—did not affect the therapeutic activity of various bsAbs. Since CD18 antibodies have been shown to be safely applicable in patients, blockade of this integrin holds promise as a potential target for the prevention of unwanted off-target T cell activation and allows the application of truly effective bsAb doses.

Lymphocyte Subpopulations in Human Malnutrition: Cytotoxic and Suppressor Cells

PEDIATRICS ◽  
1977 ◽  
Vol 59 (3) ◽  
pp. 423-427
Author(s):  
R. K. Chandra
Keyword(s):  
B Lymphocytes ◽  
Peripheral Blood ◽  
Relative Proportion ◽  
Suppressor Cells ◽  
Lymphocyte Subpopulations ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Cell Mediated Immunity ◽  
Surface Markers ◽  
And Function

Lymphocytes in the peripheral blood of young children with protein-calorie undernutrition were evalutated for surface markers and function. Thymus-dependent lymphocytes were reduced and the immunoglobulin-bearing B lymphocytes were unchanged. The relative proportion of the remaining "null" lymphoid cells was increased. Null cells and, to a lesser extent, B lymphocytes showed cytotoxic activity against xenogeneic target cells and suppressed phytohemagglutinin-induced DNA synthesis by normal T lymphocytes. It is suggested that these alterations in lymphoid subpopulations contribute to depressed cell-mediated immunity in malnutrition.

Caspase Activation Is Required for Nitric Oxide–Mediated, CD95(APO-1/Fas)–Dependent and Independent Apoptosis in Human Neoplastic Lymphoid Cells

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4311-4320 ◽  
Author(s):  
Katerina Chlichlia ◽  
Marcus E. Peter ◽  
Marian Rocha ◽  
Carsten Scaffidi ◽  
Mariana Bucur ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Present Report ◽  
Lymphoid Cells ◽  
Jurkat Cells ◽  
Target Cells ◽  
No Production ◽  
No Donor ◽  
Synthase Inhibitor ◽  
Inhibitor Of Protein Synthesis

Abstract Nitric oxide (NO), an important effector molecule involved in immune regulation and host defense, was shown to induce apoptosis in lymphoma cells. In the present report the NO donor glycerol trinitrate was found to induce apoptosis in Jurkat cells that are sensitive to CD95-mediated kill. In contrast, a CD95-resistant Jurkat subclone showed substantial protection from apoptosis after exposure to NO. NO induced mRNA expression of CD95 (APO-1/Fas) and TRAIL/APO-2 ligands. Moreover, NO triggered apoptosis in freshly isolated human leukemic lymphocytes which were also sensitive to anti-CD95 treatment. The ability of NO to induce apoptosis was completely blocked by a broad-spectrum ICE (interleukin-1β converting enzyme)-protease/caspase inhibitor and correlated with FLICE/caspase-8 activation. This activation was abrogated in some neoplastic lymphoid cells but not in others by the inhibitor of protein synthesis cycloheximide. Our results were confirmed using an in vitro experimental model of coculture of human lymphoid target cells with activated bovine endothelial cells generating NO as effectors. Furthermore, the inhibition of endogenous NO production with the inducible NO synthase inhibitor NG-monomethyl-L-arginine caused a complete abrogation of the apoptotic effect. Our data provide evidence that NO-induced apoptosis in human neoplastic lymphoid cells strictly requires activation of caspases, in particular FLICE, the most CD95 receptor-proximal caspase. Depending on the cell line tested this activation required or was independent of the CD95 receptor/ligand system.

scholarly journals DYNAMICS OF ACRIDINE ORANGE-CELL INTERACTION

1963 ◽  
Vol 18 (2) ◽  
pp. 237-250 ◽  
Author(s):  
Elliott Robbins ◽  
Philip I. Marcus
Keyword(s):  
Cell Viability ◽  
Acridine Orange ◽  
Time Course ◽  
Physiological State ◽  
Vital Staining ◽  
Cell Interaction ◽  
Extracellular Milieu ◽  
Ultimate Fate ◽  
Cell Compartmentalization

The in vitro localization of acridine orange (AO) in living cells was monitored by means of fluorescence microscopy, quantitative cell viability studies, and photofluorimetric measurements following dye-cell interaction. The parameters, pH, time, dye concentration, and the metabolic state of the cell were found to exert a profound influence on the time course and distribution of staining. The parameters studied are mutually interdependent, and intracellular dye localization may be predictably altered by their appropriate manipulation. Conditions are defined whereby two morphologically distinct but physiologically interrelated reactions, namely, acridine orange particle (AOP) formation and cytoplasmic reddening (CR) may be caused, prevented, reversed, or modified. These results are explained in terms of the facilitation or inhibition of an intracytoplasmic dye-segregating mechanism, in turn affected by the rate of dye ingress and the physiological state of the cell. Whereas the accumulation of AO in AOP is compatible with cell viability, the appearance of CR is correlated with cell death. It is pointed out that meaningful interpretation of vital staining requires precise regulation of many parameters in the extracellular milieu. A scheme of cell compartmentalization with respect to AO is proposed to satisfactorily account for the effects of environmental variations on the distribution and ultimate fate of intracellular dye. The AOP are viewed as normally present acid phosphatase-positive multivesicular bodies.

scholarly journals CELL TO CELL INTERACTION IN THE IMMUNE RESPONSE

1968 ◽  
Vol 128 (4) ◽  
pp. 855-874 ◽  
Author(s):  
W. J. Martin ◽  
J. F. A. P. Miller
Keyword(s):  
Immune Response ◽  
Cell Interaction ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Antilymphocyte Globulin ◽  
Spleen Cells ◽  
Sheep Erythrocytes ◽  
Normal Spleen ◽  
Thymus Cells

In this series of papers it has been shown that the immune response of mice to sheep erythrocytes requires the participation of two classes of lymphoid cells. Thymus-derived cells initially react with antigen and then interact with another class of cells, the antibody-forming cell precursors, to cause their differentiation to antibody-forming cells. Antilymphocyte globulin depressed the ability of mice to respond to sheep erythrocytes. This effect was more marked when the antigen was injected intraperitoneally than intravenously, and occurred only when the antilymphocyte globulin was given before or simultaneously with antigen. Injection of thymus cells restored to near normal the ability to respond to an intravenous injection of sheep erythrocytes. Spleen cells from antilymphocyte globulin-treated mice gave a weak adoptive immune response in irradiated recipients. The addition of thymus cells however enabled a response similar to that given by normal spleen cells. When thymectomized irradiated recipients were used, normal spleen cells continued to give a higher response to a challenge of sheep erythrocytes at 2 and 4 wk postirradiation than did spleen cells from ALG-treated donors. This result is more consistent with the notion that thymus-derived target cells are eliminated, rather than temporarily inactivated, by antilymphocyte globulin. These findings suggest that, in vivo, antilymphocyte globulin acts selectively on the thymus-derived antigen-reactive cells.

scholarly journals Migration ofAntigen-Specific T Cells Away from CXCR4-Binding Human ImmunodeficiencyVirus Type 1gp120

2004 ◽  
Vol 78 (10) ◽  
pp. 5184-5193 ◽  
Author(s):  
Diana M. Brainard ◽  
William G. Tharp ◽  
Elva Granado ◽  
Nicholas Miller ◽  
Alicja K. Trocha ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Active Movement ◽  
Target Cells ◽  
Cell Mediated Immunity ◽  
Cell Trafficking ◽  
Hiv 1

ABSTRACT Cell-mediated immunity depends in part on appropriate migration and localization of cytotoxic T lymphocytes (CTL), a process regulated by chemokines and adhesion molecules. Many viruses, including human immunodeficiency virus type 1 (HIV-1), encode chemotactically active proteins, suggesting that dysregulation of immune cell trafficking may be a strategy for immune evasion. HIV-1 gp120, a retroviral envelope protein, has been shown to act as a T-cell chemoattractant via binding to the chemokine receptor and HIV-1 coreceptor CXCR4. We have previously shown that T cells move away from the chemokine stromal cell-derived factor 1 (SDF-1) in a concentration-dependent and CXCR4 receptor-mediated manner. Here, we demonstrate that CXCR4-binding HIV-1 X4 gp120 causes the movement of T cells, including HIV-specific CTL, away from high concentrations of the viral protein. This migratory response is CD4 independent and inhibited by anti-CXCR4 antibodies and pertussis toxin. Additionally, the expression of X4 gp120 by target cells reduces CTL efficacy in an in vitro system designed to account for the effect of cell migration on the ability of CTL to kill their target cells. Recombinant X4 gp120 also significantly reduced antigen-specific T-cell infiltration at a site of antigen challenge in vivo. The repellant activity of HIV-1 gp120 on immune cells in vitro and in vivo was shown to be dependent on the V2 and V3 loops of HIV-1 gp120. These data suggest that the active movement of T cells away from CXCR4-binding HIV-1 gp120, which we previously termed fugetaxis, may provide a novel mechanism by which HIV-1 evades challenge by immune effector cells in vivo.

scholarly journals Induction of specific immune unresponsiveness with purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. III. Proof for the existence of autoanti-idiotypic killer T cells and transfer of suppression to normal syngeneic recipients by T or B lymphocytes.

1978 ◽  
Vol 147 (1) ◽  
pp. 63-76 ◽  
Author(s):  
H Binz ◽  
H Wigzell
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Underlying Mechanism ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Selective Suppression ◽  
Specific Receptors ◽  
T Lymphoblasts ◽  
Killer T Cells ◽  
Suppressive Mechanism

Specific immune unresponsiveness against a given set of histocompatibility antigens can be induced by immunization with autologous, antigen-specific T lymphoblasts. Such unresponsiveness can be transferred by lymphoid cells from autoblast-immunized donors to normal syngeneic recipients. The cells being most efficient in transferring the selective suppression are T lymphocytes from the spleen, especially if of Ly 1-2+3+ phenotype. By using such T lymphocytes we deem it likely that the actual underlying mechanism is one of actual transfer of autoanti-idiotypic killer T cells. In support for this view is the fact that such T cells endowed with exquisite specific, cytolytic reactivity towards autologous idiotype-positive T target cells exist in autoblast immune animals. Significant suppression may also be transferred with T cells of Ly 1+2-3- phenotype or with B cells. Here, we consider the suppressive mechanism to be one of production of autoanti-idiotypic antibodies. By using affinity fraction procedures, it was finally possible to prove that all T-cell suppressive activity resides in a population with true antigen-binding-specific receptors for the relevant idiotypes.

scholarly journals SEPARABLE POPULATIONS OF ACTIVATED THYMUS-DERIVED LYMPHOCYTES IDENTIFIED IN TWO ASSAYS FOR CELL-MEDIATED IMMUNITY TO MURINE TUMOR ALLOGRAFTS

1974 ◽  
Vol 140 (1) ◽  
pp. 267-289 ◽  
Author(s):  
Robert E. Tigelaar ◽  
R. M. Gorczynski
Keyword(s):  
Cytotoxic Activity ◽  
Velocity Sedimentation ◽  
Target Cells ◽  
Cell Mediated Immunity ◽  
Macrophage Migration ◽  
Inhibition Activity ◽  
Migration Inhibition ◽  
Spleen Cells ◽  
Macrophage Migration Inhibition

The immune response of C57BL mice to a DBA/2 tumor allograft has been assessed in two assays of cell-mediated immunity, the in vitro lysis of 51Cr-labeled target cells and the antigen-mediated inhibition of macrophage migration. Both assays were shown to be measuring a T-cell-mediated reaction. Three types of experiments suggested that distinct subpopulations of T cells mediate these reactions. The tissue distributions of these activities was distinctive; both activities were present in spleens from i.p. immunized mice, but only macrophage migration inhibition activity was found in the peripheral lymph nodes (PLN) of such mice. Adoptive transfer of immune spleen cells into irradiated syngeneic recipients revealed that while a substantial amount of migration inhibition activity could subsequently be found in PLN, cytotoxic activity was found predominantly in the spleens of these adoptive hosts. Velocity sedimentation analysis of immune cells 14 days after i.p. immunization indicated that while the majority of cytotoxic activity was associated with small and medium lymphocytes, the majority of migration inhibition activity was associated with medium and large lymphocytes. In addition, normal spleen cells were fractionated by velocity sedimentation immediately before allosensitization in vitro. Subsequent analysis of the sensitized fractions revealed that the activity profiles for cytotoxicity and macrophage migration inhibition were not coincident. The implications of these observations are discussed.

scholarly journals REJECTION OF TUMOR ALLOGRAFTS BY MOUSE SPLEEN CELLS SENSITIZED IN VITRO

1971 ◽  
Vol 133 (4) ◽  
pp. 821-833 ◽  
Author(s):  
Irun R. Cohen ◽  
Amiela Globerson ◽  
Michael Feldman
Keyword(s):  
Inhibitory Effect ◽  
Lymphoid Cells ◽  
Mouse Spleen ◽  
Target Cells ◽  
Functional Assay ◽  
Spleen Cells ◽  
Growth Of Tumor ◽  
Selection Of

This paper reports a model system of cellular immunity in which allosensitization of mouse spleen cells is induced in vitro. Allosensitization was achieved by culturing spleen cells upon monolayers of allogeneic fibroblasts. The ability of the spleen cells to inhibit the growth of tumor allografts in vivo served as a functional assay of sensitization. We found that unsensitized spleen cells or spleen cells sensitized against unrelated fibroblast antigens had no inhibitory effect on the growth of allogeneic fibrosarcoma cells when they were injected together into irradiated recipients. In contrast, spleen cells which were specifically allosensitized in vitro were found to be highly effective in inhibiting the growth of an equal number of allogeneic tumor cells. Several times more spleen cells from mice sensitized in vivo were required to produce a similar immune effect. This confirms the findings of previous studies which indicate that sensitization in cell culture can promote the selection of specifically sensitized lymphocytes. Preincubating sensitizing fibroblasts with allo-antisera blocked the allosensitization of spleen cells. This suggests that antibodies binding to fibroblasts may inhibit the induction of sensitization by competing with lymphocytes for antigenic sites. Mouse spleen cells which were able to recognize and reject tumor allografts in vivo were unable to cause lysis of target fibroblasts in vitro. Such fibroblasts, however, were susceptible to lysis by rat lymphoid cells sensitized by a similar in vitro method. These findings indicate that the conditions required for lymphocyte-mediated lysis of target cells may not be directly related to the processes of antigen recognition and allograft rejection in vivo.

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