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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous studies from this laboratory it was shown that OVA(mPEG)n conjugates induced: (i) tolerance in mice with respect to IgG and IgE antibody responses to dinitrophenylated OVA (DNP-OVA); and (ii) OVA-specific suppressor T (Ts) cells which could down-regulate a primary immune response in vivo. For the present study, we have developed an in vitro culture system for assessing the activity of Ts cells of mice tolerized by an OVA(mPEG)13 conjugate. Spleen cells from mice which had been primed with DNP4-OVA in Al(OH)3 gel were cultured with DNP4-OVA to induce a secondary antibody response in vitro. After 6 days, cells secreting anti-DNP antibodies of the IgG1 class were enumerated by an immunoenzymatic plaque-forming cell assay. Addition to the culture of T cells from mice treated with 3 i.p. injections of 500 micrograms of OVA(mPEG)13 resulted in a 29-61% reduction in the number of IgG1 anti-DNP antibody-forming cells, in comparison with the effect of T cells from mice treated with PBS. It was concluded that this tolerogenic conjugate induced splenic Ts cells which were capable of suppressing secondary in vitro anti-DNP responses.
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PMID:Down-regulation of secondary in vitro antibody responses by suppressor T cells of mice treated with a tolerogenic conjugate of ovalbumin and monomethoxypolyethylene glycol, OVA(mPEG)13. 253 91

Primary cultures of adult rat hepatocytes (Fischer 344) were used as an in vitro metabolic activation system in immunotoxicological assays. Rat hepatocytes were isolated by a collagenase perfusion technique and cultured for 20 to 24 hr to allow the formation of a monolayer on collagen-coated plastic petri dishes. Spleen cells isolated from (C57BL/6 X C3H)F1 mice were cocultured with the hepatocytes along with the chemicals. Cyclophosphamide (CP) and Aflatoxin B1 (AFB1) were effectively activated in this coculture system and produced a dose-related suppression of the in vitro antibody responses to LPS, DNP-Ficoll, and SRBC in 3 hr. Neither CP (1 mM) nor AFB1 (10(-4) M) cultured with spleen cells alone produced any effects. Both CP and AFB1 also produced a dose-related suppression of the proliferative responses to LPS, Con A, and PHA. In contrast, up to 100 mM of N-nitrosodimethylamine (DMN) did not suppress any of these assays after a 3-hr incubation in the coculture system. These results indicate that a coculture system can be used to characterize the activity of immunosuppressive chemicals requiring metabolic activation.
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PMID:Immunosuppression induced by chemicals requiring metabolic activation in mixed cultures of rat hepatocytes and murine splenocytes. 308 86

The suppression of in vitro antibody responses by dimethylnitrosamine (DMN) was produced in a mouse hepatocyte and splenocyte co-culture system. Mouse hepatocytes were isolated from female B6C3F1 mice and cultured for 20-24 hr to allow the formation of a monolayer on collagen-coated plastic petri dishes. Spleen cells were isolated from the same hybrid and were co-cultured with the hepatocytes along with DMN. Cyclophosphamide (CP), an immunosuppressive agent requiring metabolic activation that was included as an initial positive control, produced a marked suppression of the in vitro antibody responses to LPS, DNP-Ficoll, and SRBCs in 4 hr in the co-culture system. Under comparable conditions DMN markedly suppressed the response to SRBCs, marginally suppressed the response to DNP-Ficoll, and did not suppress the polyclonal response to LPS. The suppression by DMN was related to the rocking speed during the 4-hr co-culture period and was optimally produced when the cultures were not rocked. Addition of serum into the medium (10% fetal calf serum) during the co-culture period did not change the effects of DMN on the antibody response. However, the addition of extracellular DNA (1 mg calf thymus DNA/ml) prevented the suppression of the antibody response by DMN. These results suggest that DNA represents the primary macromolecular target for the reactive intermediate of DMN, and indicate that a syngeneic co-culture system can be used to characterize the in vitro immunosuppression
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PMID:Suppression of in vitro antibody production by dimethylnitrosamine in mixed cultures of mouse primary hepatocytes and mouse splenocytes. 349 64

Anti-dinitrophenyl IgE secreting hybridoma B 53 cells may be rejected when injected subcutaneously in BALB/c mice. These mice are immune as they withstand without any ill effect the intraperitoneal injection of LD100 B 53 cells. Sera from mice which rejected the tumor have cytotoxic antibodies against the hybridoma, as shown by in vitro tests, but serum cannot transfer immunity to naive BALB/c mice against hybridoma B 53. Spleen cells from mice which have rejected the tumor might transfer immunity against B 53 hybridoma, and with Winn tests it has been shown that these spleen cells are very effective against the B 53 cells and also against the myeloma cells which were used for the fusion to construct the B 53 hybridoma. Subcutaneously injected B 53 cells not only produce anti-DNP IgE secreting tumors, but often also metastasize to spleen, and they are sometimes detected in the circulating blood. Mice with splenic metastasis or with detectable circulating B 53 cells generally die. However, we did observe one mouse with splenic metastasis which successfully rejected the tumor and became immune to B 53 cells.
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PMID:Studies on immunity in hybridoma-bearing mice. B. Immunity against the hybridoma. I. Studies on the immune state of mice after rejection of the hybridoma. 396 44

Certain antigens such as polymerized flagellin are capable of producing relatively normal antibody levels in thymectomized mice, whereas others, including heterologous erythrocytes require the presence of T cells in a helper capacity. The mechanism of thymus-independent antibody production was investigated by comparing the primary IgM responses of spleen cells from ATXBM, XBM, and normal mice to various physical forms of the flagellar antigens of Salmonella adelaide in vitro. No reduction in antibody-forming cell levels to polymerized flagellin over a wide dose range was observed in ATXBM cultures, although the same spleen cells did not respond to an optimal dose of sheep red cells. In contrast, when flagellar determinants were presented in a monomeric form or as flagellin-coated donkey red cells, a highly significant difference was observed between the antibody responses of spleen cells from ATXBM mice and XBM or normal controls. The results suggested that the requirement for T cells in antibody production is not a property of specific antigenic determinants, but depends on the mode of antigenic presentation. The validity of this conclusion was confirmed by using another antigenic determinant (DNP) coupled either to the thymus-independent carrier, POL, or to the thymus-dependent carrier, DRC. Spleen cells from XBM mice produced comparable AFC levels to both forms of DNP, but the results from ATXBM cultures showed a marked difference. The anti-DNP response to DNP-DRC was greatly reduced compared to controls, whereas that to DNP-POL was normal even after prolonged thoracic duct drainage of the ATXBM donors and pretreatment of their spleen cells with anti-theta-serum and complement. The data presented here imply that the role of T cells in humoral immunity is the presentation of antigen to B cells in such a manner as to initiate optimal antibody synthesis.
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PMID:The relationship between antigenic structure and the requirement for thymus-derived cells in the immune response. 410 94

Spleen cells from mice immunized against ovalbumin (OA) or dinitrophenylated mouse serum albumin (DM) were found to be specifically cytotoxic in vitro towards target cells (chicken red blood cells) coated with these antigens. Inhibition of specific cytotoxicity was observed when free soluble antigen was added to the incubation mixtures. DM-immune cell cytotoxicity could be specifically and completely inhibited by DNP-lysine and was thus shown to be hapten specific. Complete and specific inhibition was also observed for OA-immune cell cytotoxicity using OA as inhibitor, but compared with the inhibition curves obtained with DNP-lysine, the OA cytotoxicity inhibition curves were shifted by a factor of about one hundred towards lower molar inhibitor concentrations. Very similar results were observed when the serum antibodies of DM- and OA-immune animals were analyzed by passive hemagglutination inhibition. With increasing time after immunization, both cytotoxicity inhibition curves and agglutination inhibition curves, shifted to lower antigen or hapten concentrations. Specific cytotoxicity against antigen-coated target cells was induced in nonimmune spleen cells (a) by serum from immune animals, and (b) by supernatants from in vitro immune cell cultures. In both instances, the factor which induced antigen-specific cytotoxic activity could be absorbed on anti-mouse Ig columns, thus demonstrating its immunoglobulin nature. The ability of target cell bound antibodies to induce cytotoxicity in nonimmune spleen cells was restricted to the 7S antibody class.
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PMID:Cytotoxic immune cells with specificity for defined soluble antigens. IV. Antibody as mediator of specific cytotoxicity. 412 50

Specific immunological unresponsiveness was induced using thymus-dependent antigens in congenitally athymic (nu/nu) mice, in which no T-cell function has been demonstrated. The tolerance was induced in vivo by the injection of 5-10 mg of either FGG or DNP-HGG. Spleen cells from treated mice were tested in vitro for the ability to mount thymus-independent immune responses against FGG in the presence of polymerized flagellin POL, and the DNP determinant conjugated to POL. A specific deficiency in either the in vitro anti-FGG or anti-DNP response was demonstrated, depending on the antigen used for treatment of the spleen cell donor. Athymic mice treated with FGG were also tested by in vivo challenge with FGG given with POL as an adjuvant and were found to be hyporesponsive. Unresponsiveness to in vitro challenge was established by 24 h after the in vivo injection of FGG. It was found that the injection of POL with the FGG prevented the development of unresponsiveness, but not if the POL was given 24 h or more after the FGG. The unresponsiveness could not be overcome by confrontation with allogeneic spleen cells from CBA mice, although the presence of allogeneic spleen cells had a large amplifying effect on the response of control spleen cells. These experiments demonstrate a mechanism for the tolerization of bone marrow-derived cells by thymus-dependent antigens in the absence of the thymus.
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PMID:Induction of immunological tolerance to a thymus-dependent antigen in the absence of thymus-derived cells. 413 95

Spleen cells from CBA or congenitally athymic ("nude") mice were pretreated with various concentrations of DNP coupled to a copolymer of D-glutamic acid and D-lysine (DNP(37)-D-GL), under various conditions of time and temperature. After washing, they were then cultured for 3 days with the direct B cell immunogen, DNP coupled to Salmonella adelaide flagella (DNP-FLA). Under all circumstances tried, exposure of cells to 1 microg/ml DNP-D-GL caused a 70-100% depression in the subsequent DNP-specific PFC response, and 100 ng/ml caused a lesser but still substantial effect. At the concentrations used, DNP-D-GL did not affect irrelevant antibody responses. Though cells from nude mice responded somewhat less well to DNP-FLA than those from CBA mice, no significant difference in the reaction of the two populations to the tolerogen was noted. This demonstrates that DNP-D-GL can, as previously suspected, directly cause unresponsiveness in B lymphocytes.
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PMID:Induction of B cell tolerance in vitro to 2,4-dinitrophenyl coupled to a copolymer of D-glutamic acid and D-lysine (DNP-D-GL). 457 21

Spleen cells from mice primed to trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH) generate IgG anti-TNP memory responses when stimulated in vitro with either thymus-dependent (TD) or thymus-independent (TI) forms of the hapten. When supernatants from Con A-stimulated spleen cells (Con A Sup) were added to such secondary cultures the TI responses to DNP-dextran or TNP-T4 were augmented; the TD response to TNP-KLH was suppressed. Passage over Sephadex and addition of alpha-methyl-D-mannoside did not inhibit augmentation by Con A Sup, indicating that augmentation did not result from direct action of the lectin on the responding cells. Augmentation occurred equally well in cultures that had been depleted of T cells by treatment with anti-Thy-1.2 and complement. Limiting dilution analyses revealed that Con A Sup increased the frequency of TI-responding precursors approximately threefold while causing a concomitant decrease in TD-responding precursors. To determine the relationship of the additional TI precursors and those normally detected in the absence of Con A Sup, the TI-responding IgG precursors were first eliminated through selective suicide by using DNP-dextran plus BUdR and light treatment; subsequently no TI-responding IgG PFC could be detected to DNP-dextran unless Con A Sup was also added. The data suggest Con A Sup may augment the TI responses to DNP-dextran and TNP-T4 by recruiting additional precursors from a memory cell pool formerly insensitive to these forms of antigen.
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PMID:Concanavalin A supernatant recruits antigen-insensitive IgG memory B lymphocyte precursors into an antigen-sensitive precursor pool. 617 4

The role of various subpopulations of antigen-presenting macrophages in the induction of T-lymphocyte subpopulations has been difficult to study in the past. We have used an in vitro system of bone marrow cell culture both to induce T-effector (TDH) and T-suppressor (Ts) cells active in delayed-type hypersensitivity. Bone marrow-derived macrophages (BM-MA) grown in Teflon bag cultures were allowed to attach to culture dishes and were pulse-labeled with 2,4-dinitrobenzene sulfonate (DNBSO3). Spleen cell lymphocytes from nonsensitized BALB/c mice were cocultured with antigen-pulsed or control BM-MA for 3 days. The lymphocytes were harvested, and injected iv into BALB/c mice which were challenged within 1 hr after injection by painting the right ear with 2,4-dinitrofluorobenzene (DNFB, effector test) or sensitized with DNFB on 2 days following iv injection of the cells and challenged 5 days later (suppressor test). Ear swelling was measured 24 hr later to assess the effector or suppressor function of the in vitro educated lymphocytes. BM-MA grown for 5 days (BM-MA 5) in L-cell conditioned medium induced only TDH cells (Thy 1+, Lyt 1+2-) whereas BM-MA grown for 10 days in conditioned medium induced only Ts cells (Thy 1+, Lyt 1-2+). In both cases, induced TDH and Ts cells were antigen specific. Functionally, induced Ts cells suppressed the afferent limb of the delayed response. When DNP-BM-MA 5 and DNP-BM-MA 10 were used to induce TDH or Ts cells in vivo by subcutaneous or intravenous injection respectively, only BM-MA 5 were able to sensitize recipient mice. Both 5- and 10-day macrophage populations induced Ts cells in vivo. Functionally, these Ts cells appeared to act on the efferent limb of the delayed reaction. We conclude that different populations of antigen-presenting macrophages can preferentially induce TDH or Ts cells, perhaps depending on antigen presentation in association with class II antigens or on the functional state of the antigen-presenting cell.
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PMID:Selective induction of delayed hypersensitivity T-effector and T-suppressor lymphocytes in vitro by haptenized bone marrow-derived macrophages. 623 31


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