Induction of immunologic tolerance in adult mice by repeated injection of allogenic spleen cells

1968 ◽  
Vol 66 (1) ◽  
pp. 794-795
Author(s):  
I. N. Golovistikov
1993 ◽  
Vol 128 (1) ◽  
pp. 74-80
Author(s):  
Maria A Villanua ◽  
Agnieszka Szary ◽  
Ana I Esquifino ◽  
Andrzej Bartke

This work was undertaken to study the effects of thymostimulin (TP-1) on the immune function in Ames dwarf mice, and to relate these effects to PRL and/or GH deficiency in these animals. Male Ames dwarf mice implanted with pituitaries from normal mice under the kidney capsule, sham-operated dwarf mice and normal immature or adult mice were injected daily for five days with TP-1. In comparison to normal animals, sham-operated dwarf mice had markedly lower body, thymus and spleen weights, as well as a lower number of lymphocytes in the spleen and in the thymus and the natural killer (NK) activity of spleen lymphocytes. Ectopic pituitary transplants produced the expected enhancement of body weight gain and increased spleen and thymus weights, which reached the values found in normal (non-dwarf) animals. The numbers of lymphocytes in the spleen and thymus were significantly increased in pituitary-grafted dwarf mice, but the grafts did not modify the cytotoxic activity of NK spleen cells, or the number of peripheral white blood cells (PWBC). In sham-operated dwarf mice, TP-1 treatment did not modify the number of cells in the spleen and thymus, or the NK activity. In pituitary-grafted dwarf mice, treatment with TP-1 induced an increase in the number of spleen lymphocytes and in the NK activity of spleen cells without affecting the weight of lymphoid organs or the number of thymic cells. Plasma prolactin (PRL) and growth hormone (GH) levels of pituitary-grafted dwarf mice were not changed after TP-1 administration. Surprisingly, the NK activity of spleen lymphocytes in normal adult mice was greatly increased after TP-1 administration. These findings suggest that the thymic extract TP-1 can exert a major stimulatory influence on NK activity of spleen lymphocytes in adult mice, and potentiate some of the stimulatory effects of hormones secreted by ectopic pituitary transplants on the immune function of Ames dwarf mice. These effects are not mediated by modifications of the release of PRL or GH.


1969 ◽  
Vol 130 (4) ◽  
pp. 765-775 ◽  
Author(s):  
Nathan Trainin ◽  
Myra Small ◽  
Amiela Globerson

Impaired immunological competence of spleen cells from neonatally thymectomized C57B1/6 young adult mice was apparent when these cells were tested in an in vitro graft-versus-host assay. Spleen cell inocula prepared from thymectomized mice did not induce enlargement of (C3H/eb x C57BI/6)F1 newborn spleen explants, whereas the same number of cells from intact donors consistently initiated splenomegaly. Spleen enlargement was observed, however, when the explants were challenged by cells from thymectomized donors in the presence of syngeneic thymus extract, indicating that the spleen cells in suspension attained immunological competence under the influence of a non-cellular component of the thymus. Immunocompetence was also evident when the cells from thymectomized donors were first incubated with thymus extract for 1 hr and subsequently tested for reactivity. Cells from the same thymectomized donor mice exposed in parallel to extracts from syngeneic spleen or mesenteric lymph node at an equivalent protein concentration did not initiate a graft-versus-host response. These experiments demonstrate that immune reactivity in the graft-versus-host response involves activation of lymphoid cells by a humoral factor of the thymus acting directly upon these cells.


1989 ◽  
Vol 169 (5) ◽  
pp. 1693-1701 ◽  
Author(s):  
A G Rolink ◽  
F Melchers ◽  
R Palacios

The rat mAbs R52.120 and R52.625 inhibit the action of IL-5 on both IL-5-sensitive cell lines and freshly isolated splenic B lymphocytes. Neither antibody inhibits the proliferative cell responses promoted by IL-2, IL-3, or IL-4. Purified R52.120+ lymphoid spleen cells contain 15-20-fold higher numbers of B lymphocytes responding to IL-5 in the form of maturation into antibody-producing cells. By immunofluorescence staining and flow fluorocytometry, the R52.120 and R52.625 antibodies bound to all 12 IL-5-sensitive cell lines tested. Both antibodies react with 2-4% cells in the spleen, 5% lymphoid cells, and 10-15% myeloid cells in the bone marrow, and 10-14% in the peritoneum of C57BL/6, DBA/2, and BALB/c adult mice. No positive cells for either antibody were detected in the thymus and lymph nodes of these mice. Both R52.120 and R52.625 antibodies specifically inhibit the binding of radiolabeled IL-5 to its receptor. Finally, R52.120 and R52.625 antibodies precipitate from 35S-methionine-labeled IL-5-R+ cell lysates three proteins with Mr 46,000, 130,000, and 140,000. Taken together from these results, we conclude that the R52.120 and R52.625 mAbs recognize epitopes on the IL-5-R complex very close or identical to the IL-5 binding sites.


1982 ◽  
Vol 156 (2) ◽  
pp. 567-584 ◽  
Author(s):  
D E Harris ◽  
L Cairns ◽  
F S Rosen ◽  
Y Borel

A unique experimental model is described, where natural immunologic tolerance to a well-defined soluble native antigen (murine C5) is examined in congenic strains of mice that differ only by the presence or the absence of C5. A highly sensitive hemolytic assay was developed to detect nanogram amounts of C5 as well as an assay of anti-C5 inhibition of C5 hemolytic activity. The latter was more sensitive than immunodiffusion. Two reciprocal approaches were used to study the cellular basis of tolerance in irradiated hosts of either strain. In the first, lymphoid cells from either strain were transferred to irradiated B10.D2OSN hosts that were lacking C5 and so would not hinder detection of anti-C5 antibody upon challenge with murine C5. Second, lymphoid cells from either strain were transferred to irradiated B10.D2NSN hosts, whose native C5 provided the antigenic stimulus. The immune response of whole nonadherent spleen cell suspension as well as mixtures of T and B cells (separated on the basis of surface immunoglobulin) from either strain were studied. In addition, the duration of tolerance and the antigen requirement to maintain it in irradiated C5-deficient hosts repopulated with C5-sufficient spleen cells was examined. The positive control of irradiated C5-deficient hosts repopulated with syngeneic spleen cells showed a primary and secondary response to immunization. In contrast, C5-sufficient spleen cells failed to respond both in the primary and the secondary response. Because the unresponsiveness was not caused by antigen carryover and was not antigen specific, it represents central tolerance. In C5-sufficient irradiated hosts (where immunization was not required and antigen was present in natural form and physiological concentration), transfer of C5-deficient cells mediated a drop in C5 levels to 10-20% of that noted in unreconstituted controls. T and B cell mixing experiments from the two strains into deficient or sufficient hosts demonstrated that tolerance is T cell dependent and that C5-sufficient or -deficient B cells could cooperate with nontolerant C5-sufficient T cells to produce significant anti-C5 antibody or mediate a significant drop in C5 levels. In addition, the presence of antigen was necessary to maintain tolerance. In conclusion, these results show that (a) natural tolerance to C5 is an active process that is T cell dependent and requires the presence of antigen; (b) in this natural model, clonal abortion does not seem to occur; and (c) both tolerant and nontolerant B cells retain the capacity to produce autoantibody.


2012 ◽  
Vol 178 (6) ◽  
pp. 600-603 ◽  
Author(s):  
Mimako Nakano ◽  
Yoshiaki Kodama ◽  
Kazuo Ohtaki ◽  
Nori Nakamura
Keyword(s):  

1988 ◽  
Vol 168 (2) ◽  
pp. 713-724 ◽  
Author(s):  
S Haba ◽  
A Nisonoff

We have previously shown that adult A/J mice produce high titers of anti-IgE with isotypic or idiotypic specificities in response to challenge with a conjugate of KLH with syngeneic monoclonal IgE. Thus, B cells that can synthesize anti-IgE are present in the mice. Adult mice are unresponsive to unconjugated IgE in CFA, suggesting that tolerance exists at the level of T cells. The present study shows that neonatal mice produce anti-IgE antibodies in response to unconjugated IgE in CFA, but that this capacity is lost after the age of 2-3 wk. The loss of responsiveness corresponds closely with the appearance of detectable IgE in serum, suggesting that the IgE may induce tolerance. The affinities of anti-IgE antibodies produced by neonatal mice fall in the range of values obtained with KLH-IgE in adult mice. Tolerance to unconjugated IgE in CFA can be induced in neonatal mice by administration of IgE in saline. In addition, the tolerant state can be induced by adoptive transfer of spleen cells from adult mice. The time-dependent acquisition of tolerance provides a useful model for studying mechanisms of tolerance and autoimmunity.


1974 ◽  
Vol 14 (2) ◽  
pp. 163-170 ◽  
Author(s):  
Janice Lankford ◽  
Rebecca Blackstock ◽  
Victoria Szatalowicz ◽  
Richard M. Hyde

1961 ◽  
Vol 106 (3) ◽  
pp. 472-475 ◽  
Author(s):  
F. Shapiro ◽  
C. Martinez ◽  
J. M. Smith ◽  
R. A. Good

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