scholarly journals CYTOTOXICITY BY NONIMMUNE ALLOGENEIC LYMPHOID CELLS

1967 ◽  
Vol 126 (2) ◽  
pp. 395-405 ◽  
Author(s):  
Erna Möller
Keyword(s):  
Lymphoid Cells ◽  
Primary Immune Response ◽  
Antigenic Determinants ◽  
Target Cells ◽  
Mouse Tumor ◽  
Hybrid Cells ◽  
F1 Hybrid ◽  
Target Strain ◽  
Immune Response In Vitro

Nonimmune lymphoid cells were capable of causing cytotoxicity of H-2 incompatible mouse tumor cells in vitro in the presence of PHA, whereas syngeneic cells were not. Semisyngeneic and X-irradiated (1500–3000 R) F1 hybrid lymphoid cells were cytotoxic for target cells derived from one of the parental strains. In addition, parental nonimmune and X-irradiated lymphoid cells damaged hybrid target cells. It was concluded that one component of cytotoxicity was not related to an induction of a primary immune response in vitro, since F1 hybrid cells are not capable of reacting immunologically against parental type target cells. It seemed probable that cytotoxicity was caused by target cell confrontation with antigenically and/or structurally incompatible lymphoid cells. This conclusion was strengthened by the demonstration that isoantibodies produced in the target strain and directed against the allogeneic lymphoid cells specifically suppressed cytotoxicity. Isoantibodies reacting against some but not all of the antigenic determinants of the lymphoid cells differentiating them from the target cells did not suppress cytotoxicity. The specific suppression of cytotoxicity by specific isoantibodies against the lymphoid cells support the allogeneic inhibition concept.

scholarly journals ANTIBODY AND IMMUNOGLOBULIN PRODUCTION AT THE CELLULAR LEVEL IN BURSECTOMIZED-IRRADIATED CHICKENS

1969 ◽  
Vol 129 (6) ◽  
pp. 1247-1259 ◽  
Author(s):  
Gunnar V. Alm ◽  
Raymond D. A. Peterson
Keyword(s):  
Plasma Cells ◽  
Rabbit Antiserum ◽  
Later Life ◽  
Primary Response ◽  
Lymphoid Cells ◽  
Primary Immune Response ◽  
Antigenic Determinants ◽  
Spleen Cells ◽  
Lymphoid Cell Population

The effect of bursectomy combined with sublethal X-irradiation in the newly hatched chicken on the immunoglobulin and antibody producing capacity in later life was investigated. The previous findings of a significant incidence of hypogammaglobulinemia in such animals were confirmed. Spleen cells from severely hypogammaglobulinemic animals synthesized and secreted little or no immunoglobulin. Such spleen lymphoid cells contained fewer immunoglobulin antigenic determinants than spleen cells from irradiated control animals as evidenced by their relative inability to respond by an increased DNA synthesis after in vitro culture with rabbit antiserum to chicken immunoglobulin. Therefore, the deficiency in the immunoglobulin synthesis extends not only to actively secreting cells such as plasma cells, but to the entire lymphoid cell population. As expected, most irradiated-bursectomized chickens, irrespective of plasma immunoglobulin levels failed to produce detectable amount of circulating antibodies to Brucella abortus antigen in the primary immune response. Severely hypogammaglobulinemic animals were completely unable to elaborate any plaque forming cells (PFC) in the primary response to sheep red blood cells (SRBC). The results of this investigation support the contention that in the severely hypogammaglobulinemic bursectomized-irradiated chicken the entire antibody producing and immunoglobulin producing cell line is absent. The possibility remains that precursor or stem cells are present but are not appropriately directed to antibody synthesis by other cell types.

scholarly journals CELL INTERACTIONS IN THE PRIMARY IMMUNE RESPONSE IN VITRO: A REQUIREMENT FOR SPECIFIC CELL CLUSTERS

1969 ◽  
Vol 129 (2) ◽  
pp. 351-362 ◽  
Author(s):  
Donald E. Mosier
Keyword(s):  
Immune Response ◽  
Cell Cultures ◽  
Primary Immune Response ◽  
Antigenic Determinants ◽  
Specific Cell ◽  
Spleen Cells ◽  
Sheep Erythrocytes ◽  
Cell Clusters ◽  
Immune Response In Vitro

Mouse spleen cells were found to associate in cell clusters during the primary immune response to sheep erythrocytes in vitro. About 10% of the cell clusters had the following unique properties; (a) they contained most, if not all, antibody-forming cells, (b) they contained only cells forming antibody to one antigen when cell cultures were immunized with two antigens, (c) the cells in clusters reaggregated specifically after dispersion, and (d) the specific reaggregation of clusters appeared to be blocked by antibody to the antigen. The integrity of cell clusters was required for the proliferation of antibody-forming cells, and prevention of clustering by mechanical means or by excess antibody blocked the immune response. Antibody and antigenic determinants on the surfaces of cells probably provide the basis for interaction. The unique microenvironment of cell clusters was essential for the primary immune response in vitro.

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.

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 Streptococcal-induced cell-mediated-immune destruction of cardiac myofibers in vitro.

1977 ◽  
Vol 146 (2) ◽  
pp. 344-360 ◽  
Author(s):  
L C Yang ◽  
P R Soprey ◽  
M K Wittner ◽  
E N Fox
Keyword(s):  
Antigenic Determinants ◽  
Target Cells ◽  
Heart Cells ◽  
Guinea Pig Heart ◽  
Whole Cells ◽  
Group A ◽  
Streptococcal Antigens ◽  
Lymphocyte Cytotoxicity

We have demonstrated that T lymphocytes from the spleens of adult guinea pigs sensitized to group A streptococcal antigens are cytotoxic for cultured fetal guinea pig heart cells. Lymphocyte cytotoxicity, measured by 51Cr release from target cells, was stimulated by sensitization in vivo with group A whole cells, cell walls, and purified protoplast membranes emulsified with complete Freund's adjuvant (CFA). Sensitization with group C streptococcal antigens in CFA or CFA alone produced lymphocytes with little or no specific cytotoxic activity. Target cells of cultured fetal skeletal muscle, liver, or skin were relatively refractory to effector cell cytotoxicity. The presence of antigenic determinants on the membranes of cultured myofibers, cross-reacting with group A streptococcal cellular antigens, was confirmed by immunofluorescence. These data are discussed in terms of a model for poststreptococcal rheumatic myocarditis in which cell-mediated autoimmune mechanisms may participate.

scholarly journals IgE class-restricted tolerance induced by neonatal administration of soluble or cell-bound IgE. Cellular mechanisms.

1984 ◽  
Vol 160 (4) ◽  
pp. 953-970 ◽  
Author(s):  
S S Chen ◽  
F T Liu ◽  
D H Katz
Keyword(s):  
Tolerance Induction ◽  
Suppressor Cells ◽  
Mouse Cell ◽  
Lymphoid Cells ◽  
Soluble Form ◽  
Antigenic Determinants ◽  
Antigen Specificity ◽  
Cellular Mechanisms ◽  
Neonatal Treatment

Certain aspects of the phenomenon of IgE class-restricted tolerance induced in mice by neonatal treatment with monoclonal IgE, either in soluble form or coupled to syngeneic spleen cells, were examined. The present studies document that this tolerance results from exposure to IgE molecules, irrespective of their antigen specificity, and the resulting effects are polyclonal in nature since IgE responses directed against antigenic determinants unrelated to the tolerance-inducing IgE molecules are affected. Moreover, such findings indicate that the molecular subregion(s) responsible for inducing IgE class-restricted tolerance resides in the epsilon heavy chain constant region domain(s) of IgE. When soluble IgE is employed, tolerance induction results from neonatal treatment with doses as low as 2.5 micrograms per injection per mouse; cell-bound IgE is considerably more potent, in terms of total dose required, since tolerance results from treatment with as few as 1 X 10(6) cells per injection (per mouse), equivalent to an absolute quantity of 0.2 ng of IgE per injection. This long-term class-specific tolerance appears to be a unique feature of the IgE antibody system, since treatment of mice with monoclonal antibodies of the IgA, IgG1, or IgG2b isotypes, either in soluble or cell-bound form, does not perturb antibody responses of their corresponding isotypes or in the IgE class. By analyzing the lymphoid cells of IgE-tolerant mice after they reached adulthood, the following observations were made: (a) lymphoid cells from such tolerant mice fail to develop FcR epsilon + cells upon in vitro stimulation with IgE, as is characteristically observed with lymphoid cells from nontolerant mice; and (b) mice rendered tolerant by neonatal treatment with soluble IgE possess IgE class-restricted suppressor T cells, demonstrable in adoptive transfer experiments, whereas no such suppressor cells are evident in mice in which cell-bound IgE was used for neonatal treatment. The latter observations could mean that two different mechanisms underlie the IgE class-restricted tolerance, or both mechanisms operate coordinately to varying degrees depending upon which regimen is used for tolerance induction, as discussed herein.

scholarly journals ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS

1972 ◽  
Vol 135 (3) ◽  
pp. 567-578 ◽  
Author(s):  
J. Wayne Streilein
Keyword(s):  
Graft Versus Host Disease ◽  
Lymphoid Cells ◽  
Antigenic Determinants ◽  
F1 Hybrid ◽  
Host Disease ◽  
Syrian Hamsters ◽  
Graft Versus Host ◽  
Refractory State ◽  
Lymphocyte Transfer ◽  
Additional Support

The so-called refractory state, one sequela of acute graft-versus-host disease, has been studied in adult (CB x MHA)F1 hybrid Syrian hamsters inoculated with sublethal numbers of MHA-anti-CB lymphoid cells. Intracutaneous challenge of these animals with 200 million MHA-anti-CB lymphoid cells after the acute syndrome subsided failed to evoke epidermal necrolysis, whereas a similar challenge administered to normal F1 recipients invariably resulted in lethal epidermolysis. Moreover, the gradual attrition of lymphatic tissues in these hosts and their fading capacity to display adequately immune lymphocyte transfer reactions in the skin coincided with increasing evidence of host refractoriness, suggesting a causal interrelationship. It was possible to circumvent refractoriness by challenging these animals intracutaneously with MHA-anti-CB cells if: (a) the hosts had been lethally irradiated and reconstituted with F1 hematopoietic cells, or (b) the intracutaneous inocula contained admixed F1 lymphoid cells. This evidence provides additional support for the hypothesis that in GVH disease donor lymphocytes attack primarily host lymphoid cells bearing offending homologous antigens. The GVH process can continue so long as these lymphocyte-bound antigens persist within the host, and will abate only as the aggregate host lymphatic mass is effectively destroyed (hamsters) or its antigenic determinants are masked by isoantibodies (rats, mice, man?). At this point, insufficient target tissues remain for rechallenge to incite significant recrudescence of the disease.

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.

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

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.

Sign in / Sign up

Export Citation Format

Share Document