scholarly journals In vitro generation of cytotoxic lymphocytes against radiation- and radiation leukemia virus-induced tumors. III. Suppression of anti-tumor immunity in vitro by lymphocytes of mice undergoing radiation leukemia virus-induced leukemogenesis.

1980 ◽  
Vol 152 (6) ◽  
pp. 1473-1483 ◽  
Author(s):  
E Yefenof ◽  
A Meidav ◽  
E Kedar
Keyword(s):  
Leukemia Virus ◽  
Suppressor Cells ◽  
Cytotoxic Lymphocytes ◽  
Suppressor T Cells ◽  
Induced Tumors ◽  
High Incidence ◽  
X Irradiation ◽  
Radiation Induced ◽  
Cytotoxic Responses

Adult C57BL/6 mice exposed to fractionated irradiation or inoculated with the radiation leukemia virus (RadLV), develop high incidence (80-100%) of lymphatic leukemias within 3-6 mo. RadLV-induced lymphomas can elicit cytotoxic responses in vitro in lymphocytes of preimmunized syngeneic mice, a reaction that is dependent on the expression of membrane-associated viral antigenicity. As soon as 5 d after RadLV inoculation, and during the entire leukemogenic process, suppressor T cells are detectable in the spleen that are capable of specifically abrogating generation of syngeneic anti-tumor cytotoxic cells in vitro. Mice exposed to fractionated x irradiation do not develop suppressor cells and their splenocytes may be stimulated in vitro to generate cytotoxicity toward RadLV-induced leukemias. These findings suggest that although RadLV has been isolated from radiation-induced leukemias, x-ray- and RadLV-induced leukemogenesis do not seem to involve a common viral etiology, and that induction of suppressor cells during RadLV leukemogenesis may be essential for tumor progression.

scholarly journals LEUKEMIA-ASSOCIATED TRANSPLANTATION ANTIGENS RELATED TO MURINE LEUKEMIA VIRUS

1973 ◽  
Vol 138 (3) ◽  
pp. 593-606 ◽  
Author(s):  
H. Sato ◽  
E. A. Boyse ◽  
T. Aoki ◽  
C. Iritani ◽  
L. J. Old
Keyword(s):  
Leukemia Virus ◽  
Leukemia Cells ◽  
F1 Hybrids ◽  
Mouse Strains ◽  
Cytotoxicity Test ◽  
High Incidence ◽  
Radiation Induced ◽  
Repeated Passage

Two BALB radiation leukemias are strongly rejected by hybrids of BALB with certain other mouse strains, although BALB mice themselves exhibit no detectable resistance whatever. Hybrids immunized with progressively increased inocula are resistant to 200 x 106 or more leukemia cells; their serum is cytotoxic for the leukemia cells in vitro and protects BALB mice against challenge with these BALB leukemias. The antigenic system thus identified has been named X.1. In (BALB x B6) hybrids the major determinant of resistance was shown to be a B6 gene in the K region of H-2. This is likely to be the Rgv-1 (Resistance to gross virus) locus of Lilly, which may thus be identified in this case as an Ir (Immune response) allele conferring ability to respond to X.1 antigen on MuLV and leukemia cells, and so responsible for production of X.1 antibody and the rejection of X.1+ leukemia cells by hybrid mice. Immunoelectron microscopy with X.1 antiserum (from immunized hybrids) shows labeling both on the cell surface and on virions produced by the leukemia cells. It is not known whether X.1 comprises only one or more than one antigen. Three radiation-induced BALB leukemias, one A strain radiation-induced leukemia, and 15/15 AKR primary spontaneous leukemias were typed X.1+ by the cytotoxicity test. Several other leukemias, including one induced by passage A Gross virus and one long-transplanted AKR ascites leukemia carried in (B6 x AKR)F1 hybrids, were X.1-. Normal mice of strains with a high incidence of leukemia and one other strain (129) express X.1 antigen, but evidently in amounts too small for certain detection in vitro; by the method of absorption in vivo, however, these strains could be typed X.1+ and other strains X.1-. We ascribe the X.1 antigen system tentatively to a sub-type of MuLV that is not passage A Gross virus and is probably not the dominant sub-type in strains with a high incidence of leukemia. After repeated passage in hybrids, one of the BALB leukemias became relatively resistant to rejection by the hybrid, partially lost its sensitivity to X.1 antiserum in vitro, and in electron micrographs was seen to produce fewer virions. The serum of untreated (BALB x B6) hybrids often contains cytotoxic antibody against leukemia cells, some of it probably anti-X.1. But another commonly occurring antibody, which is cytotoxic for C57BL leukemia EL4, appears to belong to another (undefined) system.

scholarly journals Mechanisms of idiotype suppression. I. In vitro generation of idiotype-specific suppressor T cells by anti-idiotype antibodies and specific antigen.

1979 ◽  
Vol 149 (6) ◽  
pp. 1371-1378 ◽  
Author(s):  
B S Kim
Keyword(s):  
T Cells ◽  
Specific Antigen ◽  
Suppressor Cells ◽  
Culture Period ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Myeloma Protein ◽  
Specific Suppressor T Cells

Normal BALB/c spleen cells are unresponsive in vitro to the phosphorylcholine (PC) determinant in the presence of anti-idiotype antibodies specific for the TEPC-15 myeloma protein (T15) which carries an idiotypic determinant indistinguishable from that of most anti-PC antibodies in BALB/c mice. The possibility that idiotype-specific suppressor cells may be generated during the culture period was examined by coculturing the cells with untreated syngeneic spleen cells. Cells that had been preincubated with anti-T15 idiotype (anti-T15id) antibodies and a PC-containing antigen, R36a for 3 d, were capable of specifically suppressing the anti-PC response of fresh normal spleen cells, indicating that idiotype-specific suppressor cells were generated during the culture period. The presence of specific antigen also appeared to be necessary because anti-T15id antibodies and a control antigen, DNP-Lys-Ficoll, were not capable of generating such suppressor cells. Suppressor cells were induced only in the population of spleen cells nonadherent to nylon wool and the suppressive activity was abrogated by treatment with anti-Thy 1.2 serum and complement. These results indicate that anti-idiotype antibodies and specific antigen can generate idiotype-specific suppressor T cells in vitro. These in vitro results may reflect in vivo mechanisms of idiotype suppression.

Mouse one-cell embryos undergoing a radiation-induced G2 arrest may re-enter S-phase in the absence of cytokinesis

2002 ◽  
Vol 80 (7) ◽  
pp. 618-624 ◽  
Author(s):  
P Jacquet ◽  
J Buset ◽  
J Vankerkom ◽  
S Baatout ◽  
L de Saint-Georges ◽  
...  
Keyword(s):  
Calyculin A ◽  
Embryonic Cells ◽  
G2 Arrest ◽  
Cell Stage ◽  
Chromosome Fragments ◽  
X Irradiation ◽  
Radiation Induced ◽  
Mouse Zygotes ◽  
The One

PCC (premature chromosome condensation) can be used for visualizing and scoring damage induced by radiation in the chromatin of cells undergoing a G1 or G2 arrest. A method involving the fusion of irradiated single embryonic cells with single MI oocytes was used to induce PCC in mouse zygotes of the BALB/c strain, which suffer a drastic G2 arrest after X-irradiation (dose used 2.5 Gy). Other G2-arrested embryos were exposed in vitro to the phosphatase inhibitor calyculin A. Both methods furnished excellent chromosome preparations of the G2-arrested embryos. The mean number of chromosome fragments did not change significantly during G2 arrest, suggesting that zygotes of this strain are unable to repair DNA damage leading to such aberrations. Forty to fifty percent of the irradiated embryos were unable to cleave after G2 arrest and remained blocked at the one-cell stage for a few days before dying. PCC preparations obtained from such embryos suggested that about 30% of them had undergone a late mitosis not followed by cytokinesis and had entered a new DNA synthesis. These results are discussed in the light of recent observations in irradiated human cells deficient in the p53/14-3-3sigma pathway.Key words: PCC, embryo, oocyte, calyculin A, G2 arrest, cytokinesis.

scholarly journals GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (3) ◽  
pp. 648-659 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Stuart Schlossman ◽  
Baruj Benacerraf
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Suppressor Cells ◽  
Specific Response ◽  
Spleen Cells ◽  
X Irradiation

In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice. Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-θ serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained θ-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.

Strong selection for cells containing new ecotropic recombinant murine leukemia virus provirus after propagation of C57BL/6 radiation-induced thymoma cells in vitro or in vivo

1983 ◽  
Vol 3 (9) ◽  
pp. 1675-1679
Author(s):  
P Jolicoeur ◽  
E Rassart ◽  
P Sankar-Mistry
Keyword(s):  
Cell Lines ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Primary Radiation ◽  
Secondary Tumors ◽  
Radiation Induced ◽  
Viral Sequences ◽  
Murine Leukemia

Using the Southern procedure, we have studied the presence of ecotropic-specific murine leukemia viral sequences in genomic DNA isolated from primary X-ray-induced thymomas, from lymphoid cell lines established from them, or from secondary tumors passaged in vivo. We found that primary radiation-induced thymomas and infiltrated spleens do not harbor newly acquired ecotropic provirus. However, additional ecotropic proviruses (which appear recombinant in the gagpol region) could be detected in most of the tumorigenic cell lines established in vitro from them and in tumors arising from subcutaneous transplantation of the primary thymomas. These results suggest that primary radiation-induced thymomas may not be clonal. They also indicate a strong correlation between the presence of ecotropic recombinant proviruses in the genome and the growth ability, both in vitro and in vivo, of specific cells within these thymomas, suggesting a possible mitogenic function for murine leukemia virus.

scholarly journals BIOLOGICAL EXPRESSIONS OF LYMPHOCYTE ACTIVATION

1973 ◽  
Vol 137 (3) ◽  
pp. 649-659 ◽  
Author(s):  
Robert R. Rich ◽  
Carl W. Pierce
Keyword(s):  
Cell Population ◽  
Concanavalin A ◽  
Lymphocyte Activation ◽  
Suppressor Cells ◽  
Mouse Spleen ◽  
Spleen Cells ◽  
Cell Responses ◽  
Helper Cells ◽  
X Irradiation

A population of thymus-derived lymphocytes has been identified that, upon activation by the nonspecific plant mitogen concanavalin A, suppresses the development of plaque-forming cell responses in fresh or 48-h antigen-stimulated cultures of mouse spleen cells. Suppressor cells can inhibit both primary and secondary IgM and IgG responses in vitro. X-irradiation before activation of peripheral thymus-derived cells by concanavalin A abrogates generation of suppressor cells. After a 48 h activation period, however, the function of concanavalin A-activated suppressor cells is radioresistant. As yet uncertain is whether these suppressor cells are a population of cells distinct from thymus-derived "helper" cells. In certain important regards, the cells mediating these two opposing functions share similar characteristics; the effect observed may be determined by the circumstances of activation or the numbers of activated cells, and may consequently represent different functions of a single thymus-derived regulator cell population.

scholarly journals Targeting MICA/B with cytotoxic therapeutic antibodies leads to tumor control

2021 ◽  
Vol 1 ◽  
pp. 107
Author(s):  
Mathieu Bléry ◽  
Manel Mrabet-Kraiem ◽  
Ariane Morel ◽  
Florence Lhospice ◽  
Delphine Bregeon ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Tumor Control ◽  
Cytotoxic Lymphocytes ◽  
Drug Conjugates ◽  
Induced Tumors ◽  
Human Igg1 ◽  
Induced Proteins ◽  
Optimal Tumor

Background: MICA and MICB are tightly regulated stress-induced proteins that trigger the immune system by binding to the activating receptor NKG2D on cytotoxic lymphocytes. MICA and MICB are highly polymorphic molecules with prevalent expression on several types of solid tumors and limited expression in normal/healthy tissues, making them attractive targets for therapeutic intervention. Methods: We have generated a series of anti-MICA and MICB cross-reactive antibodies with the unique feature of binding to the most prevalent isoforms of both these molecules. Results: The anti-MICA and MICB antibody MICAB1, a human IgG1 Fc-engineered monoclonal antibody (mAb), displayed potent antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) of MICA/B-expressing tumor cells in vitro. However, it showed insufficient efficiency against solid tumors in vivo, which prompted the development of antibody-drug conjugates (ADC). Indeed, optimal tumor control was achieved with MICAB1-ADC format in several solid tumor models, including patient-derived xenografts (PDX) and carcinogen-induced tumors in immunocompetent MICAgen transgenic mice. Conclusions: These data indicate that MICA and MICB are promising targets for cytotoxic immunotherapy.

scholarly journals Suppressor T cells activated in a primary in vitro response to non-major histocompatibility alloantigens.

1982 ◽  
Vol 156 (5) ◽  
pp. 1398-1414 ◽  
Author(s):  
S Macphail ◽  
O Stutman
Keyword(s):  
Mixed Lymphocyte Reaction ◽  
Cytotoxic T Lymphocyte ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Normal Spleen ◽  
In Vitro Response

Normal mouse spleen cells are not capable of mounting a primary cytotoxic T lymphocyte (Tc) response to non-H-2 alloantigens in vitro, although a good secondary H-2-restricted response is observable after in vivo immunization of the responder animals. Suppressor cells are generated in such a primary responses provided a Mls incompatibility exists between the responder and stimulator. These suppressors are not antigen specific, are Thy-1+, Lyt-1+, 2-, I-J-, and are highly radiosensitive. The suppressor cell precursors in normal spleen express the same phenotype. These suppressor cells are probably implicated in the lack of a primary Tc response in a primary mixed lymphocyte reaction across non-H-2 incompatibilities that include an Mls difference.

scholarly journals Expansion of monocytic myeloid-derived suppressor cells ameliorated intestinal inflammatory response by radiation through SOCS3 expression

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
You Yeon Choi ◽  
Ki Moon Seong ◽  
Hyun Jung Lee ◽  
Seung Sook Lee ◽  
Areumnuri Kim
Keyword(s):  
Radiation Exposure ◽  
Intestinal Inflammation ◽  
Immune Therapy ◽  
Suppressor Cells ◽  
Clinical Problem ◽  
Myeloid Derived Suppressor Cells ◽  
Therapy Targets ◽  
Socs3 Expression ◽  
Radiation Induced

AbstractRadiation-induced colitis is a common clinical problem after radiation therapy and accidental radiation exposure. Myeloid-derived suppressor cells (MDSCs) have immunosuppressive functions that use a variety of mechanisms to alter both the innate and the adaptive immune systems. Here, we demonstrated that radiation exposure in mice promoted the expansion of splenic and intestinal MDSCs and caused intestinal inflammation due to the increased secretion of cytokines. Depletion of monocytic MDSCs using anti-Ly6C exacerbated radiation-induced colitis and altered the expression of inflammatory cytokine IL10. Adoptive transfers of 0.5 Gy-derived MDSCs ameliorated this radiation-induced colitis through the production IL10 and activation of both STAT3 and SOCS3 signaling. Intestinal-inflammation recovery using 0.5 Gy-induced MDSCs was assessed using histological grading of colitis, colon length, body weight, and survival rate. Using in vitro co-cultures, we found that 0.5 Gy-induced MDSCs had higher expression levels of IL10 and SOCS3 compared with 5 Gy-induced MDSCs. In addition, IL10 expression was not enhanced in SOCS3-depleted cells, even in the presence of 0.5 Gy-induced monocytic MDSCs. Collectively, the results indicate that 0.5 Gy-induced MDSCs play an important immunoregulatory role in this radiation-induced colitis mouse model by releasing anti-inflammatory cytokines and suggest that IL10-overexpressing mMDSCs may be potential immune-therapy targets for treating colitis.

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