scholarly journals PRODUCTION OF IMMUNOLOGICAL TOLERANCE IN MICE AFTER REPEATED INJECTIONS OF DISRUPTED SPLEEN CELLS

1963 ◽  
Vol 118 (5) ◽  
pp. 743-758 ◽  
Author(s):  
C. Martinez ◽  
J. M. Smith ◽  
M. Blaese ◽  
R. A. Good

1. Tolerance of male skin isografts has been regularly produced in female mice of the C57B1 strain sublines 1, 4, and 6 during adult life by repeated injection of completely disrupted spleen cells derived from male donors. The tolerant state is long-lasting since such grafts have remained in place more than 9 months. 2. Prolonged survival of homotransplants of skin has regularly been produced in DBA/2 mice during adult life by repeated injections of completely disrupted spleen cells from Balb/C donors. When injections of disrupted spleen cell material are continued over a sufficiently long period, permanent acceptance of the skin homografts may be obtained between these strains. 3. Immunological tolerance across even the strong H-2 histocompatibility barrier was obtained in the neonatal period and during adult life by repeated injection of disrupted spleen cell preparations. The tolerant state has been revealed by both mammary adenocarcinoma and skin homografting across this strong histocompatibility barrier. 4. In contradistinction to the tolerant state produced by injection of intact spleen cells in neonatal animals or during adult life or that produced by parabiotic union, the tolerance produced by repeated injection of disrupted spleen cell preparations cannot be transferred to syngenic neonatal mice with spleen cells of the tolerant animal. 5. The implications of these findings in transplantation biology and in consideration of the basic nature of tolerance are discussed.

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Masaji Okada ◽  
Yoko Kita ◽  
Noriko Kanamaru ◽  
Satomi Hashimoto ◽  
Yasushi Uchiyama ◽  
...  

Objective. Our aim was to investigate the effects of IL-6 blockade on the progression ofMycobacterium tuberculosis(TB) and compare them with those of TNF-αblockade in mice.Methods. Mice were intravenously infected with TB and injected with antibodies. Survival was monitored and histological and immunological studies were carried out.Results. All anti-IL-6R Ab-treated mice and 8 of 10 control mice survived until sacrificed 224 days after TB challenge, whereas anti-TNF-αAb-treated mice all died between 120 and 181 days. Anti-IL-6R Ab-treated mice exhibited no significant differences in TB CFU in organs, including the lungs, and no deterioration in histopathology compared to control mice at 4 weeks. In contrast, anti-TNF-αAb-treated mice exhibited increased TB CFU and greater progression of histopathological findings in organs than control mice. Spleen cells from anti-TNF-αAb-treated mice had decreased antigen-specific response in IFN-γrelease and proliferation assays. The results in anti-IL-6R Ab-treated mice suggest that spleen cell responses were decreased to a lesser degree. Similar results were obtained in IL-6 knockout (KO) mice, compared with TNF receptor 1 (TNFR1) KO and TNFR1/IL-6 double KO (DKO) mice.Conclusion. IL-6R blockade promotes the progression of TB infection in mice far less than TNF-αblockade.


Blood ◽  
1985 ◽  
Vol 65 (4) ◽  
pp. 990-996
Author(s):  
I Fabian ◽  
D Douer ◽  
L Levitt ◽  
Y Kletter ◽  
PL Greenberg

Mitogen-stimulated murine spleen cells produce humoral substances capable of supporting murine hematopoiesis and pluripotent stem cell proliferation in vitro. Thus, we evaluated conditioned media generated by human spleen cells (SCM) in the presence or absence of mitogens for factors stimulatory for human pluripotent (CFU-GEMM), erythroid (BFU- E), and myeloid (CFU-GM) precursors. Two and one half percent to 10% SCM stimulated proliferation of all three types of precursor cells from nonadherent buoyant human marrow target cells. Mitogen-stimulated SCM augmented CFU-GM (175% to 225%), whereas CFU-GEMM and BFU-E growth was essentially unchanged. Cell separation procedures used to determine which cells provided these microenvironmental stimuli indicated that nonadherent mononuclear spleen cells provided the bulk of the CSF-GM, whereas adherent cells (95% nonspecific esterase + monocyte- macrophages) and nonadherent cells provided similar proportions of CSF- mix and erythroid burst-promoting activity (BPA). The nonadherent cells generating high levels of CSF-mix, BPA, and CSF-GM were predominantly Leu-1-negative, ie, non-T, cells. In the presence or absence of mitogens, SCM was a more potent source (1.3- to 3.8-fold) than peripheral leukocyte CM of the growth factors for the three progenitor cell types. Specific in situ cytochemical stains for analyzing morphology of myeloid colonies demonstrated that SCM stimulated the proliferation of the same types and proportions of colonies as human placental CM, suggesting that these CMs may contain similar CSF-GMs. These data show the contribution of spleen cell subsets to the generation of hematopoietic growth factors and the responsiveness of these cells to various mitogenic stimuli.


Blood ◽  
1980 ◽  
Vol 55 (3) ◽  
pp. 489-493 ◽  
Author(s):  
SH Bartelmez ◽  
WH Dodge ◽  
DA Bass

Abstract Nonadherent spleen cells of mice infected with Trichinella spiralis released growth stimulatory factors (GSFs) in vitro when challenged with excretory/secretory products of muscle stage larvae. The assay of GSF was based on proliferation of normal, nonadherent syngeneic marrow cells in liquid tube cultures. Media conditioned for 1 day by challenged spleen cells stimulated eosinophil production but failed to stimulate production of other cell types. In contrast, media conditioned for 5 days supported eosinophil, neutrophil, and macrophage production. The kinetics of cell production were also different. Eosinophil production started within 1 day, reached a peak at day 2, and was down to control levels by day 4. In contrast, neutrophil/macrophage production began between 2 and 4 days and reached a peak at 6--8 days. The short duration of eosinophil production was evidently due to depletion of growth-factor-responsive cells.


1979 ◽  
Vol 25 (9) ◽  
pp. 1087-1093 ◽  
Author(s):  
Carol Wells ◽  
Edward Balish

Spleen cells from germfree rats, conventionally reared rats, and gnotobiotic rats associated with two Pseudomonas species gave no positive blastogenic response when incubated with each of four lipopolysaccharide (LPS) preparations from Escherichia coli, with glycolipid extracted from Salmonella minnesota R595 or with S. minnesota R595 lipid A. However, spleen cell preparations from athymic mice demonstrated a positive blastogenic response when incubated with E. coli LPS. Removal of adherent cells from germfree and conventional-flora rat spleen cells did not increase the mitogenic activity of LPS for nonadherent cells (< 0.5% esterase-positive cells). All rat spleen cell preparations gave positive blastogenic responses to phytohemagglutinin and concanavalin A. This study indicates that LPS may not be a mitogenic agent for rat spleen cells.


1982 ◽  
Vol 155 (5) ◽  
pp. 1491-1500 ◽  
Author(s):  
D S Vaithilingam ◽  
A A Axelrad

We have investigated the activities of alloantisera produced in B6 (C57BL/6) and B6.S strain mice reciprocally immunized with unwashed bone marrow and spleen cell suspensions from their respective Fv-2 congenic partner strains, B6.S and B6. These antisera inhibited the formation of colonies by the late erythrocytic progenitors (CFU-E) in plasma cultures seeded with unwashed bone marrow or spleen cells; washed cells were unaffected. Erythropoietic burst formation by the early progenitors (BFU-E) was not significantly inhibited by the antisera, whether the cells were washed or unwashed. We conclude (a) that the congenic antisera are capable of recognizing alloantigens controlled by alleles of Fv-2 or of a closely linked gene locus on chromosome 9; (b) that these alloantigens are situated on the surface of erythrocytic progenitor cells and can be removed by washing; and (c) that the expression of the alloantigens on these cells is influenced by their stage of differentiation.


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