Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that glial cells from mice resistant or susceptible to the autoimmune disease experimental allergic encephalomyelitis (EAE) may differ in their abilities either to express Ia antigens and/or stimulate anti-class II (Ia)-specific T-cells. Ia antigens were induced on glial cells from EAE-susceptible (SJL/J) and -resistant (B10.S and DBA/2) strains of mice by culture with lymphokines from activated T-cells (2 degrees SN). Ia antigen expression was quantified with an enzyme-linked immunosorbent assay (ELISA) in which glia were exposed to monoclonal anti-Ia antibodies and alkaline phosphatase-labeled anti-mouse Ig antibodies. The ability of glial cells to stimulate anti-Ia T-cells was quantified by culturing irradiated glial cells with anti-Ia-specific T-cell lines and measuring the amounts of [3H]thymidine incorporated by these lines. Glial cells from all strains of mice could be induced to express Ia antigens and upon exposure to high concentrations of lymphokines, amounts of expressed Ia antigen were equivalent. However, at limiting lymphokine concentrations, glia from the EAE-resistant strain B10.S expressed greater amounts of Ia antigen than did glia from SJL/J mice (p less than 0.05), suggesting that B10.S glia were more sensitive to the Ia-inducing effects of T cell lymphokines. In contrast to the above results, glia from EAE-susceptible SJL mice consistently demonstrated an increased ability to induce T-cell proliferation in lines specific for Ias antigen, compared to glia from EAE-resistant mice, even those of the same Ia haplotype (i.e. B10.S). Spleen cells from resistant strains had equivalent and frequently greater ability to induce anti-Ia-specific T-cell proliferation than did SJL spleen cells. These data suggest (a) that there are differences in the sensitivity of glia from different strains of mice to the Ia antigen-inducing effects of T-cell lymphokines, (b) that expression of Ia antigen does not necessarily correlate with the ability to stimulate Ia-specific T-cells, (c) that there are organ-specific differences in the ability to stimulate Ia antigen-specific T-cells, and (d) that an additional variable involved in determining resistance or susceptibility to an organ-specific autoimmune disease may be the ability of the target organ to stimulate anti-Ia-specific T-cells.
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PMID:Immunologic differences in murine glial cells and their association with susceptibility to experimental allergic encephalomyelitis. 229 81

The cytolytic responses of C3H/HeJ mice after 50% hepatectomy (PH) were assessed in a 4-hr 51Cr-release assay. Spleen cells (SC) (50 x 10(6] from normal or PH C3H/HeJ (H-2k) mice were sensitized with equal numbers of irradiated allogeneic DBA/2 (H-2d) spleen cells in a five-day mixed lymphocyte culture. Generated cytolytic activity was measured against 51Cr-labeled P815 mastocytoma (H-2d) and EL4 lymphoma (H-2b) target cells. The wet weight and cell numbers per spleen following 50% partial hepatectomy were 70% and 75% higher than the control values for the first 20 days, and then returned to normal levels by 21 days. The cytolysis by spleen cells from 2-, 14-, and 31-day PH mice were 89.3 +/- 0.7, 86.9 +/- 5.3, and 90.1 +/- 1.3%, respectively, compared with control (sham-operated) values of 56.0 +/- 1.0, 57.0 +/- 2.0, and 49.9 +/- 7.0% (P less than 0.03 at E/T 100:1). This enhanced cytolysis by PH spleen cells remained high for at least 118 days after the liver resection before returning to control levels by 268 days. Cytolytic effector cells in PH SC were generated at least 24 hr earlier than in control SC. When normal and PH cytolysis were compared following primary and secondary in vitro sensitization, the cytolytic levels of primarily-sensitized PH spleen cells were comparable to secondarily sensitized normal spleen cells. Furthermore, the primarily sensitized normal spleen cells did not show crossreactive cytolysis with EL4 target cells (H-2b), while both the primarily sensitized PH spleen cells and the secondarily sensitized normal spleen cells were significantly cross-reactive against the third party EL4 target cells. Adherent PH spleen cells appear to be responsible for this augmented cytolytic capacity since their coculture with normal nonadherent responder spleen cells increased control cytolysis by approximately 30%. These studied demonstrate that, following 50% partial hepatectomy, there is an immediate and sustained increase in the allospecific cytolytic response.
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PMID:Augmentation of cell-mediated cytotoxicity following 50% partial hepatectomy. 231 18

Spleen cells from an AKR/J X DBA/2J F1 mouse immunized with NZB/BIN spleen cells were fused with SP2/0-Ag14. Two hybrid cell lines, B220-1 and B220-2, were established that secreted antibody to the B-lineage specific B220 antigen. B220-1 and B220-2 are present on 45-55% of splenic and bone marrow lymphocytes and absent from thymus. By flow cytometry, all immunoglobulin-bearing cells were stained by these monoclonal antibodies. Although these monoclonals do not stain thymocytes, they do react weakly with Lyt-2+ peripheral T cells. Dual parameter analysis of B lymphocytes using RA3-3A1 or 14.8 show that these monoclonals recognized the same population. Prior incubation with RA3-3A1 or 14.8 was unable to completely block the binding of B220-1 or B220-2, implying that the epitopes recognized are different from the previously described monoclonal antibodies. Immunoprecipitation of the splenic lymphocyte reveals a molecule which migrates on SDS-PAGE as a single band with MW of 220,000 daltons. Expression of the distinct antigens recognized by B220-1 and B220-2 varied among mouse strains, indicating previously unappreciated polymorphism of the B220 molecule. These monoclonals are useful for cytotoxic elimination of B cells and for three-color flow cytometry.
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PMID:Differentiation antigen on murine B lymphocytes defined by monoclonal antibodies. 243 5

Nine daily intravenous (iv) injections of RA-700 (an antitumor cyclic hexapeptide) at doses of 2 to 6 mg/kg/day caused increases of WBC counts at 4-6 days after treatment in normal C57BL/6 X DBA/2 (BDF1) mice. The percentages of neutrophils and lymphocytes were modified. There was a decrease of colony-forming units in culture (CFUc) in bone marrow to 40% of the control value on day 1 but CFUc rapidly returned to normal values on day 3. The colony-forming units in spleen (CFUs) in bone marrow decreased during treatment. On the other hand, CFUc and CFUs in spleen were increased from the initiation of treatment to the time prior to the increase of WBC count. Spleen weight increased after treatment, and histologically, increases of immature and also mature granulocytes and megakaryocytes were observed. However, RA-700 did not stimulate the progress of hematoprogenitors in vitro. The results indicated that RA-700 stimulates the progress of hematoprogenitors in the spleen, but this effect is probably indirect.
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PMID:Leukocytosis in mice following therapy with a novel antitumor agent, RA-700. 249 62

Lymphocytes of autoimmune mice have been reported to have defective IL-2 production and proliferation in response to the mitogen concanavalin A. We have examined transcription of lymphokine genes in Con A stimulated spleen cells from both autoimmune and normal mice and found that IL-2, IL-4 and gamma-interferon (IFN gamma) were induced in all mice tested. Spleen cells were taken from young (pre-disease) or old (clinically active) MRL/lpr (lpr) and male BXSB autoimmune mice and from their normal counterparts (MRL/n, BXSB females, BALB/c and DBA/2) and stimulated with Con A. Con A induced production of IL-2, IL-4 and IFN gamma message and protein, and kinetics of induction did not vary significantly among the strains. However, in old lpr mice, levels of IL-2 protein and mRNA were about 10-fold lower than in other strains; IL-4 protein and mRNA were decreased approximately three-fold; and IFN gamma mRNA was readily detected in unstimulated cells and low but detectable levels of protein were produced constitutively. In contrast, little or no defect in IL-2 or IL-4 transcription or secretion were seen in male BXSB mice and no constitutive IFN gamma transcription was seen in this strain. These data indicate that all three lymphokine genes are activated by Con A in autoimmune mice, even though Con A-induced proliferation is defective in these mice. Furthermore, autoimmune mouse strains vary in terms of lymphokine expression: male BXSB mice display a normal lymphokine profile, whereas lpr mice show a marked imbalance of lymphokines compared to normal controls.
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PMID:Expression of lymphokine genes in splenic lymphocytes of autoimmune mice. 250 45

The highly metabolized nitrosourea carmustine (BCNU) is an anticancer agent which alkylates DNA and is metabolized to both active and inactive species by cytochrome P-450 enzymes. Other highly metabolized anticancer drugs have altered toxicities when some histamine H2 antagonists are coadministered. To test this hypothesis with BCNU, DBA/2J male mice were given a single injection of cimetidine (CMT 100 mg/kg) or ranitidine (RNT 25 mg) at various times up to 30 min before, or up to 60 min after a BCNU injection. Spleen colony assays for normal bone marrow stem cell viability showed enhanced toxicity for BCNU when CMT was administered concomitantly. In P-388 leukemia-bearing DBA/2J mice, both CMT and RNT significantly enhanced the antitumor effects of BCNU doses of 30 mg/kg. Pharmacokinetic analyses of BCNU elimination in Cd-1 mice showed marked prolongation of BCNU elimination and increased (BCNU concentration) x time products when CMT was concomitantly administered. These results demonstrate that enhanced BCNU bone marrow toxicity and antitumor activity is produced by CMT. The effect appears to be related to impaired drug clearance when the two agents are administered concurrently. RNT slightly enhanced BCNU antileukemic effects, but it did not significantly alter BCNU myelotoxicity nor drug elimination patterns.
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PMID:H2-antagonists and carmustine. 256

A new B-lymphoma cell line (DEAU-cell line) was established from a diffuse large-cell lymphoma (centroblastic type) and was successfully grafted in athymic nude mice. Monoclonal antibodies (MoAbs) were generated using splenocytes of DEAU-tumor bearing mice. Before the fusion experiments, cellular immunity of the mice bearing growing DEAU tumors was restored by injection of spleen cells from conventional Balb/C mice. Spleen cells from conventional Balb/C mice immunized with DEAU-cell line were also used for the generation of MoAbs. Four MoAbs (DBB.42 and DBA.44 from normal Balb/C mice, and DNA.7 and DND.53 from athymic nude mice) were investigated because they identified B-cell-associated antigens not destroyed by fixatives. DBB.42 recognized a pan-B cell-associated antigen (molecular weight (mol wt) = 45 Kd). DBA.44 detected a B-cell antigen (mol wt not determined) expressed on a subpopulation of B lymphocytes in the mantle zone of lymphoid follicles. DNA.7 also defined a B-cell antigen (43 Kd) mainly expressed on germinal center cells. Similarly, DND.53 recognized a B-cell antigen (two bands of mol wt 20 Kd and 35 Kd, respectively) mainly expressed on germinal center cells and mantle zone lymphocytes and interdigitating reticulum cells in the paracortical area. Major differences were found in the reactivities of these MoAbs on malignant lymphomas. DBB.42 was positive with almost all B-cell lymphomas and some T-cell lymphomas. Within the group of low-grade B-cell lymphomas, DBA.44 reacted principally with hairy-cell leukemia. DNA.7 reacted mainly with high-grade B-cell lymphomas with a weak positivity in low-grade B-cell lymphomas. DND.53 reacted with all but one B-cell lymphoma, cells of histiocytosis X, and Reed-Sternberg cells. These findings indicate that new MoAbs can be generated by using spleen cells from athymic mice bearing human tumors as well as by new lymphoid cell lines. The MoAbs so generated, as in the present study, are deemed potentially useful for the recognition of B-cell lymphomas in routine diagnostic histopathology. In addition, DND.53 could be of value for the diagnosis of histiocytosis X and the detection of Reed-Sternberg cells in Hodgkin's disease.
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PMID:Production of anti-B monoclonal antibodies (DBB.42, DBA.44, DNA.7, and DND.53) reactive on paraffin-embedded tissues with a new B-lymphoma cell line grafted into athymic nude mice. 267 17

In previous studies it was found that BALB/c (H-2d) was more susceptible than (BALB/c X A)F1 (H-2d X H-2a) to a tumor bearing multiple mismatched minor histocompatibility antigens, the DBA/2 (H-2d) mastocytoma P815, and that this resistance was H-2 linked. In the present studies the immunologic basis of this effect was examined by comparing the cytotoxic-T-lymphocyte (CTL) responses of BALB/c with those of (BALB/c X A)F1. Despite the BALB/c X A)F1's 34-fold greater resistance to P815 in vivo, the numbers of effector cell precursors were found to be similar in the two hosts as shown by (a) similar anti-P815 CTL responses in vitro with T-cell growth factor, (b) similar secondary anti-DBA/2 MiHA responses after in vivo priming with irradiated P815, and (c) similar frequencies of anti-DBA/2 CTL precursors by limiting-dilution analysis. However, priming with proliferating P815 in vivo revealed a defect in the BALB/c animals: Spleen cells from such animals were unable to control the growth of contaminating P815 cells in vitro or to mount strong secondary CTL responses to DBA/2 antigens. The defective priming of BALB/c could be corrected when DBA/2 spleen cells were added to the P815 inoculum. This impaired priming by living tumor cells was not seen in (BALB/c X A)F1. It is concluded that the use of living P815 tumor cells revealed a defect in immunoregulation in BALB/c mice, which rendered them susceptible to tumor growth in spite of apparently adequate numbers of anti-minor-CTL precursors. How the additional H-2 products expressed in the (BALB/c X A)F1 might correct this defect is discussed.
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PMID:Differential resistance to growth of a tumor expressing incompatible minor alloantigens reflects regulatory influences rather than differences in anti-minor-CTL-P frequencies. 285 96

Spleen cells from DBA/2 mice, after immunization with syngeneic P815 mastocytoma cells and Corynebacterium parvum, respond to P815 in vitro with a brisk, secondary-type generation of cytotoxic cells. This cytotoxicity is mediated by antigen-specific T-lymphocytes and correlates with resistance to in vivo challenge. This model confirms the observations of previous investigators made in semisyngeneic hosts using an in vivo transfer model. Spleen cells from "early" tumor-bearing hosts (TBHs), 7-12 days after intradermal (i.d.) inoculation of 10(6) P815 cells alone, made a similar, but generally higher, cytotoxic T-lymphocyte (CTL) response in vitro. Spleen cells from "late" TBHs (18-28 days) completely suppressed the in vitro CTL response of immune cells (e.g., from 71% specific release in controls down to 8% at an effector: target ratio of 40:1). Early i.d. TBH spleen cells, because of their higher level response, appeared to be resistant to this suppression (85% release for controls and 84% when suppressor cells were added at 40:1). By testing early TBH CTL at lower effector: target ratios, however, suppression by late TBH spleen cells could be readily demonstrated. When TBHs were inoculated s.c. instead of i.d. or with lower doses of tumor cells, responses were lower and susceptibility of splenic CTLs to suppression was increased. At intermediate times after tumor inoculation (14-20 days), spleen cells from TBHs still can respond in vitro, but they are completely suppressed by spleen cells from late TBHs. The suppressor cells are antigen-specific, radiation-sensitive, Thy1+ cells.
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PMID:Tumor-specific suppressor T-cells which inhibit the in vitro generation of cytolytic T-cells from immune and early tumor-bearing host spleens. 293 51

We have previously shown that YC8, a Moloney virus-induced BALB/c lymphoma, is susceptible to lysis by BALB/c anti-DBA/2 effector cells. To further evaluate the relationship between non-H-2 antigens of DBA/2 background and tumor-associated determinants, we investigated the pattern of cytotoxic and proliferative responses induced in BALB/c mice by immunization with YC8 lymphoma. Spleen cells from tumor-immunized animals were restimulated in vitro with YC8 cells and tested for cytotoxicity on target cells of different strains and haplotypes. Cytotoxicity was observed only against YC8, DBA/2 blasts, and P815 (a DBA/2 mastocytoma). BALB/c anti-YC8 effectors were equally blocked by unlabeled YC8 and P815 cells when assayed on YC8 labeled targets. A clonal analysis, however, revealed the existence of at least two types of effectors, one lytic for both P815 and YC8 cells, the other lytic for YC8 cells only. BALB/c anti-YC8 cells proliferate when stimulated both with YC8 and DBA/2 cells in the presence of accessory cells. When tested in an adoptive transfer assay, anti-YC8 cells given i.v. cured 100% of i.v. and 75% of i.p. tumor-injected mice, respectively. When given i.p. anti-YC8 effectors cured 100% of i.p. tumor-injected animals. These results confirm the expression of non-H-2, DBA/2-like antigens on the BALB/c lymphoma YC8 and reveal the presence of additional tumor-associated determinants; both sets of antigens may induce a cellular immune response and elicit immune lymphocytes which can eradicate YC8 cells in an adoptive immunotherapy assay.
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PMID:Analysis of the cellular immune response to and adoptive immunotherapy of a BALB/c lymphoma that cross-reacts with normal DBA/2 cells. 293 37


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