Production of immunological tolerance in adult mice to protein antigen with the aid of antilymphocytic serum

1973 ◽  
Vol 76 (2) ◽  
pp. 964-966
Author(s):  
O. A. Karasik ◽  
B. N. Sofronov
Keyword(s):  
Immunological Tolerance ◽  
Protein Antigen ◽  
Antilymphocytic Serum ◽  
Adult Mice

scholarly journals IMMUNE MECHANISMS IN PARABIOSIS INTOXICATION

1964 ◽  
Vol 119 (4) ◽  
pp. 567-579 ◽  
Author(s):  
Henry R. Hilgard ◽  
Eugene A. Cornelius ◽  
Agustin P. Dalmasso ◽  
Carlos Martinez ◽  
Robert A. Good
Keyword(s):  
Parental Strain ◽  
Immunological Tolerance ◽  
The Other ◽  
Term Survival ◽  
F1 Hybrid ◽  
Immunological Mechanism ◽  
Adult Mice ◽  
Hybrid Mice ◽  
Normal Hybrid

When A strain mice are placed in parabiotic union with (A x C57Bl/1)F1 hybrid partners, the parental strain partners are polycythemic and the hybrids anemic from the 5th through the 16th parabiosis days. All hybrids develop clinical intoxication between the 7th and the 12th days, and no pairs survive to 1 month. Long-term survival of parabiotic pairs can be achieved if lethally irradiated or specifically tolerant parental strain mice are united to hybrid partners. Production of tolerance by either of these methods results in elimination of anemia-polycythemia by the 12th parabiosis day and prevents intoxication in the hybrid partners. Preimmunization of the parental strain partners against the C57Bl/1 component of the hybrid leads to a considerable intensification of day 5 anemia-polycythemia. Intoxication develops in the hybrid partners between the 4th and the 6th days after union. It is concluded that anemia is primarily responsible for the syndrome of clinical intoxication. Early anemia-polycythemia on day 5 does not depend upon an immunological mechanism, but the late anemia-polycythemia appearing between days 12 and 16 is a function of the ability of the parental strain mouse to react immunologically against its hybrid partner. When neonatally thymectomized A strain mice are joined to hybrid partners, anemia-polycythemia is sustained through the 16th day and the hybrid partners develop clinical intoxication. On the other hand, when both partners are neonatally thymectomized, late anemia-polycythemia is considerably reduced, and the hybrid partners apparently do not develop clinical intoxication. It is concluded that normal hybrid mice are capable of reconstituting the immunological capacity of their thymectomized partners, whereas thymectomized hybrid mice do not have this restorative capacity. These findings are discussed in terms of their possible application to the problem of the induction of immunological tolerance in adult mice by the parabiosis procedure.

scholarly journals Spleen cells from animals tolerant to a thymus-dependent antigen can be activated by lipopolysaccharide to synthesize antibodies against the tolerogen.

1976 ◽  
Vol 143 (6) ◽  
pp. 1429-1438 ◽  
Author(s):  
G Möller ◽  
E Gronowicz ◽  
U Persson ◽  
A Coutinho ◽  
E Möller ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Immunological Tolerance ◽  
Cell Tolerance ◽  
Normal Numbers ◽  
Spleen Cells ◽  
B Cell Tolerance ◽  
Adult Mice ◽  
Protein Conjugate

Immunological tolerance was induced in adult mice by the injection of 5 mg of deaggregated hapten-protein conjugate. The tolerant state was confirmed 4-19 days later by the failure of such animals to mount an immune response against an aggregated form of the same thymus-dependent hapten-protein conjugate as well as by the inability of spleen cells from tolerant animals to respond to a thymus-independent hapten-carrier conjugate. Even though the animals were fully tolerant, their spleen cells were activated by lipopolysaccharide (LPS) in vitro to produce normal numbers of plaque-forming cells against the hapten. The finding that spleen cells from tolerant animals could be activated by LPS into synthesis of antibodies against the tolerogen indicates that tolerance to thymus-dependent antigens does not affect B cells, but presumably only T cells. It is suggested that the only stringent test for the existence of B-cell tolerance is the inability of polyclonal B-cell activators to activate antibody synthesis against the tolerogen. The findings make it unlikely that B-cell tolerance to autologous thymus-dependent antigens exists and further indicate that such antigens cannot deliver activating or tolerogenic signals to B cells, although they are competent to combine with and block the Ig receptors.

Induction of specific immunological tolerance of homografts in adult mice by sublethal irradiation and injection of donor-type spleen cells in high dosage

1962 ◽  
Vol 156 (963) ◽  
pp. 280-288 ◽  
Keyword(s):  
Immunological Response ◽  
Immunological Tolerance ◽  
Third Party ◽  
Skin Grafts ◽  
Spleen Cells ◽  
Adult Mice ◽  
Donor Type ◽  
Central Inhibition ◽  
Lymph Node Cells ◽  
Sublethal Irradiation

Adult A -strain mice in the weight-range 15 to 20 g were irradiated to 350 or 500 r, followed by the injection, divided between the intravenous and intraperitoneal routes, of suspensions of spleen cells obtained from CBA or ( CBA x A ) F 1 mice, donors and recipients being matched for sex. After the lapse of 18 to 25 days all mice, including control batches which had received irradiation but not spleen cells, were challenged with donor-type skin grafts. Mice irradiated to 500 r which received CBA spleen cells in doses from 500 to 1500 million developed severe graft-versus-host disease, fatal in most cases. Rejection of the grafts occurred in irradiated controls after periods ranging from 8 to 23 days. Mice receiving 500r followed by ( CBA x A ) F 1 spleen cells showed prolonged survival of skin grafts, amounting to 90 days or more in animals which had received the highest dose of cells (12 x 10 9 ). Analysis of the phenomenon by means of Simonsen’s discriminant spleen assay showed that approximately 85% of the immunologically competent spleen cells of the graft-bearing animals were replaced by cells of donor origin; the remainder, however, retained the power to react immunologically against third-party ( C 57 BL ) antigens. It was also possible to secure adoptive rejection of grafts by injection of 60 to 90 million A -strain lymph node cells pre-sensitized against CBA . It is concluded that the state of specific unresponsiveness induced in the adult A strain mice represented a specific central inhibition of the mechanism of immunological response and could thus be equated to immunological tolerance as classically defined. Prior splenectomy not only abolished the tolerance phenomenon, but actually reversed it, there being clear signs of an immunity resulting from the irradiation and injection procedure. This result is discussed in terms of the significance of antigen dose-level for the induction of tolerance.

scholarly journals THE PROVOCATION OF LATENT LYMPHOCYTIC CHORIOMENINGITIS VIRUS INFECTIONS IN MICE BY TREATMENT WITH ANTILYMPHOCYTIC SERUM

1968 ◽  
Vol 127 (2) ◽  
pp. 327-339 ◽  
Author(s):  
Mogens Volkert ◽  
Claus Lundstedt
Keyword(s):  
Considerable Increase ◽  
Latent Infection ◽  
Lymphocytic Choriomeningitis ◽  
Antilymphocytic Serum ◽  
Virus Infections ◽  
Adult Mice ◽  
Antibody Titers ◽  
Sublethal Doses ◽  
High Virus ◽  
Very High

The hypothesis that treatment with antilymphocytic serum (ALS) can provoke latent virus infections has been investigated. In adult mice infections with sublethal doses of LCM virus usually result in the development of immunity to the virus and at the same time to a prolonged latent infection. In the experiments described an intensive treatment with large doses of ALS was given to mice which had recovered from LCM virus infection. At the beginning of the treatment the mice had high titers of complement-fixing antibodies in their blood and no detectable virus. The data presented show that in spite of the immunity the ALS treatment provoked the occult virus and led to the development of viremia in all the treated mice. In some, very high virus titers were demonstrable. When the ALS treatment was discontinued the viremia disappeard again. In most of the mice the ALS did not suppress the complement-fixing antibody titers and in some there was even a considerable increase in titer. In such cases the increases in virus titers and in antibody titers were closely related to one another. These results demonstrate once again that the complement-fixing antibodies to the LCM virus in mice probably do not influence the virus.

scholarly journals Demonstration of an antibody-mediated tolerance state and its effect on antibody affinity.

1975 ◽  
Vol 141 (2) ◽  
pp. 411-426 ◽  
Author(s):  
G Birnbaum ◽  
M E Weksler ◽  
G W Siskind
Keyword(s):  
Immune Suppression ◽  
Single Injection ◽  
Significant Degree ◽  
Suppressive Effect ◽  
Immunological Tolerance ◽  
Spleen Cells ◽  
Antibody Affinity ◽  
High Affinity ◽  
Adult Mice ◽  
Protein Conjugate

We have described a model of immunological tolerance induced, in adult mice, by a single injection of a moderate dose of a hapten-protein conjugate. The data suggest that the mechanism of this tolerance state is the production of small amounts of high affinity antibody in response to the tolerance-inducing antigen injection. This antibody acts to inhibit the response to a subsequent challenge with antigen in complete Freund's adjuvant by a mechanism comparable to that of passive antibody-medicated immune suppression. It was shown that a small but high affinity. Tolerance was not terminated by transfer of normal syngeneic spleen or peritoneal cells into tolerant animals. Spleen cells from tolerant mice, when transferred into lethally irradiated, syngeneic animals, produced a PFC response which is greater in magnitude and tolerance state had a significant degree of carrier specificity which was shown to be comparable to the carrier specificity of antibody-mediated immune suppression. hus, evidence was presented to show that one mechanism of tolerance in adult animals in the suppressive effect of small amounts of high affinity antibody formed in response to the tolerizing injection of antigen.

Protective Action of Polyinosinic-Polycytidylic Acid in Virus and Transplanted Leukemias of the Mouse

1973 ◽  
Vol 59 (3) ◽  
pp. 167-179
Author(s):  
Luigi Chieco-Bianchi ◽  
Dino Collavo ◽  
Giovanni Biasi ◽  
Alfonso Colombatti
Keyword(s):  
Protective Action ◽  
Immunological Tolerance ◽  
Leukemic Cells ◽  
Poly I:C ◽  
Immune Reactivity ◽  
Cell Transplant ◽  
Adult Mice ◽  
Polycytidylic Acid ◽  
Polyinosinic Polycytidylic Acid

The inhibitory effects of polynucleotides on leukemia development and transplantability have been studied. RFM/Un mice, injected neonatally with leukemogenic Graffi virus, received 0.02 mg polyinosinic-polycytidylic acid (Poly I:C) intraperitoneally, twice a week, for two months starting 24 hrs after virus injection. Leukemia incidence in treated mice was significantly reduced, i.e., 56% with a mean latent period of 19 weeks as compared to 87% and 15 weeks latency in the control animals. RFM/Un adult mice, injected intravenously with different cell doses of two transplantable syngeneic leukemias, received four doses of 0.1 mg Poly I:C on alternate days starting 24 hrs after cell transplant. The evaluation of neoplastic nodules on the spleen surface according to the method of Bruce and Van Der Gaag (2) was the parameter of leukemic growth. Mice receiving Poly I:C showed a marked reduction in spleen nodule counts for all cell doses of both leukemia lines and histological examination of the spleen confirmed actual decrease in leukemic foci and disclosed enlargement of germinal centers and periarteriolar areas of lymphoid follicles. To investigate whether Poly I:C is capable of abolishing the state of immunological tolerance (operationally speaking) to cellular virus-induced antigens (CBA x C57BL)F1 adult mice, injected neonatally with Graffi virus, received 0.20 mg Poly I:C i.p. together with 104 or 105 cells from a syngeneic transplantable leukemia originally induced by Graffi virus. No differences in leukemic deaths were observed between Poly I:C treated virus-injected animals and controls, even though normal mice receiving Poly I:C and 10* cells showed 50% survival compared to 0% in control groups. Leukemic cells incubated in vitro in HE-MEM containing 0.1, 1, 10 or 100 μg Poly I:C/ml for 2, 4, 8 and 24 hrs (37 °C, 5% CO2) did not exhibit significant changes in viability as evaluated by phase contrast microscopy. On the basis of present and previous results (6), the possible mechanisms of antineoplastic action exerted by polynucleotides are discussed. It is concluded that while interferon production by synthetic RNAs may represent a major inhibiting factor in virus-induced tumors, non specific stimulation of immune reactivity and direct effect on cell metabolism and replication may play a significant role in other neoplastic conditions.

Binucleate Spermiogenesis in the Mouse

1972 ◽  
Vol 30 ◽  
pp. 112-113
Author(s):  
John J. Wolosewick
Keyword(s):  
Electron Microscopy ◽  
Phosphate Buffer ◽  
Seminiferous Epithelium ◽  
Mouse Testis ◽  
Germinal Epithelium ◽  
Intercellular Bridges ◽  
Adult Mice ◽  
Cervical Dislocation ◽  
Human And Mouse

Classically, the male germinal epithelium is depicted as synchronously developing uninucleate spermatids conjoined by intercellular bridges. Recently, binucleate and multinucleate spermatids from human and mouse testis have been reported. The present paper describes certain developmental events in one type of binucleate spermatid in the seminiferous epithelium of the mouse.Testes of adult mice (ABP Jax) were removed from the animals after cervical dislocation and placed into 2.5% glutaraldehyde/Millonig's phosphate buffer (pH 7.2). Testicular capsules were gently split and separated, exposing the tubules. After 15 minutes the tissue was carefully cut into cubes (approx. 1mm), fixed for an additional 45 minutes and processed for electron microscopy.

Sign in / Sign up

Export Citation Format

Share Document