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)

A preliminary characterization of the immunopharmacological profile of the new immunomodulating agent FCE20696 (6H,6[2-(dimethylamino)-ethoxycarbonyl]-dibenzo[b,d]pyran-HCl) was performed in mice. Single i.p. doses of this chemical, concomitantly given with the antigen, increased the antibody response and decreased the delayed hypersensitivity reaction to a suboptimal dose of SRBC, the active doses ranging from 6.25 to 50 mg/kg. No activity was observed using a full antigen dose. Macrophage cytotoxic activity was enhanced 2-4 days after a single i.p. treatment with 50 and 10 mg/kg. Spleen cell proliferation to T and B mitogens was inhibited by a single dose of 30 mg/kg given i.p. 6 days before the test, or by 10 mg/kg x 3 days ending one day before the test. Finally, generation of suppressor cells was enhanced by the compound, given p.o. biweekly for at least 7 weeks, at doses ranging from 0.1 to 10 mg/kg. Collectively taken, these data suggest that FCE20696 has a broad range of immunomodulating activities and that macrophages and suppressor cells are presumed to be the main targets of its pharmacological activity.
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PMID:FCE20696, a new synthetic immunomodulator: immunopharmacological profile. 253 74

Immunomodulatory effects of cholera toxin (CT) were investigated in a murine model using various immunological parameters. C3H/HeN mice were injected with 2 micrograms of CT at various intervals (from 6 h to 21 days) before the immunological assays. Thymocytes were markedly decreased in their absolute number, and the phenotypes in such cells were clearly shifted from Thy1.2high+ PNAhigh+ to Thy1.2low+ PNAlow+ 2-4 days after the CT treatment. Spleen T cells were relatively increased, while surface IgM positive B cells were rather decreased. Natural killer activity and in vivo and in vitro cytotoxic T lymphocyte activity were markedly suppressed during the early stages after the CT treatment but recovered completely within 21 days. Mixed lymphocyte reaction was profoundly suppressed at least for the 1st week after the CT treatment. Furthermore, EL-4 tumor of C57BL/6 origin grew progressively and killed the recipient C3H mice when such tumor cells were inoculated 6 h after the CT treatment. On the contrary, a marked augmentation of direct (IgM) and indirect (IgG) plaque-forming cell responses to sheep red blood cells was seen after CT treatment. Delayed footpad reaction to SRBC was also augmented after CT treatment. As the mechanisms, both direct augmentation of CD4+ T cells and direct suppression of CD8+ T cells appeared to occur at a time due to the CT treatment. An indirect effect of CT through the release of the endogenous steroids was dismissed in the present study. Taken together, CT appears to have differential immunomodulatory effects on various immune effector cells through various mechanisms.
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PMID:Immunomodulatory effects of cholera toxin in mice. 279 14

A temporal relationship has been demonstrated between persisting immune complexes and non-antigen-specific immunodepression. Mice were given intraperitoneal injections of Bordetella pertussis at weekly intervals. After 7 weeks they developed circulating immune complexes, the levels of which increased with continued administration of pertussis. The increase in immune complex levels was accompanied by a diminished primary immune response to intraperitoneally injected sheep erythrocytes (SRBC) as judged by a reduction in their direct and indirect plaque-forming cell response and serum agglutination titres. Spleen cells from immunodepressed pertussis-treated mice were transferred to irradiated normal recipients and displayed a normal response to SRBC. By contrast, spleen cells transferred from normal donors to irradiated pertussis-treated recipients had an impaired response to SRBC. Thus, the immunodepression caused by pertussis treatment is a property of the environment and not the lymphocytes themselves. It is considered that chronic circulating immune complexes induced by pertussis administration may cause non-antigen-specific immunodepression.
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PMID:Relationship between non-antigen-specific immunodepression and persisting immune complexes induced by pertussis in mice. 287 21

Spleen cells from CBA/J mice infected with Neisseria meningitidis displayed depressed in vitro plaque-forming cell (PFC) responses to T-dependent (sheep red blood cell; SRBC) and T-independent (TNP-LPS, TNP-Ficoll) antigens. The inhibition was observed over a wide range of antigen concentrations. The decreased responsiveness of splenocytes from infected mice was due to a selective impairment of B-cell function since helper-T-cell activity was intact in infected mice as shown by the ability of T-enriched lymphocytes to cooperate with normal B-enriched lymphocytes in the generation of an anti-SRBC response, accessory macrophage function was preserved since adherent spleen cells from bacteria-injected mice were shown to produce normal or increased levels of IL-1 and were able to cooperate with normal non-adherent spleen cells in the generation of PFC against SRBC. Addition of peritoneal cells from normal animals or extraneous IL-1 both failed to restore normal PFC responses in cultures of splenocytes from infected mice. Finally, B-enriched lymphocytes from infected mice produced poor anti-SRBC responses when cultured with either Con A supernatant or T-enriched lymphocytes from normal or infected mice. Cell-mixing experiments failed to detect the presence of suppressor cells in cultures of unfractionated spleen cells or B-enriched lymphocytes from infected mice. Therefore, the immunological unresponsiveness associated with a Neisseria meningitidis infection was attributed to a meningococcus-induced defect(s) in B-cell function. In vivo polyclonal B-cell activation leading to clonal exhaustion did not play a major role in the depression of humoral responses since meningococcal infection induced little or no polyclonal Ig secretion.
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PMID:Selective impairment of B cell function by Neisseria meningitidis. 294 9

Spirogermanium is a metal-containing compound reported to have antitumor, antiarthritic, antimalarial and immunoregulatory activity. In this study we have demonstrated that spirogermanium inhibited antibody synthesis to sheep red blood cells in BDF1 mice in vivo. Spleen cells from these treated mice were unable to respond to this antigen in vitro, and suppressed both the antibody response of normal cells to SRBC and the mitogenic response of normal cells to Concanavalin A in co-culture assays. The cells responsible for this suppression did not belong to the T cell lineage since treatment with anti-Thy-1.2 antiserum and complement did not abrogate the suppression. The suppressor cells were found to be radiation resistant and nylon wool adherent. Plastic adherence or passage over Sephadex G10 partially removed the suppression indicating the contribution, at least in part, of a suppressor macrophage. The plastic non-adherent population of cells also contained suppressor cells which were detected following anti-thy-1.2 treatment and selection by panning on anti-IgG coated plates. Fluorescent antibody and flow cytometry technology showed the population of suppressor cells to be 90% immunoglobulin positive, indicative of a B cell lineage.
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PMID:Suppressor cell induction by the anticancer drug spirogermanium. 295 34

Immune response and suppressor cell activity of CBA (H-2k) mice made tolerant to allogeneic C57B1/6 (H-2b) heart graft were studied in graft-versus-graft reaction (GvGR). Intact CBA spleen cells inhibited response of (CBA X C57B1/6)F1 cells to antigenic stimulus (sheep red blood cells--SRBC), when injected together into lethally irradiated (CBA X C57B1/6)F1 mice. Spleen cells of tolerant mice were unable to decrease immune response of (CBA X C57B1/6F1 lymphocytes to SRBC and suppressed specifically the inhibition induced by intact CBA spleen cells. Spleen cells from tolerant mice were also capable of suppressing GvGR induced by CBA lymphocytes immune to C57B1/6 cells. Pretreatment of tolerant spleen cells with rabbit antithymocyte globulin and complement before adoptive transfer diminished markedly the suppression. The results obtained in the study suggest that suppression of transplantation immunity in this model is mostly due to T suppressor cells.
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PMID:[Suppressors of the graft vs graft reaction in tolerance to alloantigens]. 296 19

Studies from this laboratory have demonstrated that incubation of murine alveolar macrophages (AM) with SRBC-primed spleen cells (SC) results in suppression of the in vitro plaque-forming cell (PFC) response and that suppression is mediated by a soluble factor contained in supernatants obtained from cultures of AM and SC. In the present study, immunological techniques employing monoclonal antibody (MoAb) were used to isolate various T-cell subsets in order to determine the phenotype of the cells which interact with AM to produce suppression. Spleen cell populations depleted of Thy-1+-, Lyt-1+-, L3T4+-, or I-J+-bearing cells failed to generate suppressive supernatants when cultured with AM. Depletion of Lyt-2+ T-cells (the classical suppressor/effector subset) did not alter the ability of the remaining cell population to cooperate with AM for generation of suppressive supernatants. Direct suppression of the PFC response in cultures containing AM was abrogated after treatment of the spleen cells with anti-I-J, but not anti-Lyt-2 MoAbs. Reconstitution of the AM-mediated suppressive response with enriched populations of SC required the presence of T-cells which expressed Lyt-1, L3T4, and I-J. These results suggest the existence of an unusual suppressor pathway involving I-J restriction but which appears to be mediated by the interaction of AM with a population of T-cells that expresses surface markers characteristic of T-helper cells.
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PMID:Cell interactions in alveolar macrophage-mediated suppression of the immune response: an unusual suppressor pathway involving a population of T-cells that express Lyt-1, L3T4, and I-J. 297 57

Mice immunized intramuscularly with a low dose, viable inoculum of C. psittaci survived an otherwise lethal intraperitoneal challenge with the homologous chlamydial strain. Immunized animals were not protected from intraperitoneal challenge by the unrelated pathogen, Listeria monocytogenes. Spleen cells from animals that exhibited protective immunity were suppressed in their proliferative responses to mitogens or chlamydial antigen in an in vitro blastogenic assay. This suppression was transferable to normal spleen cells by adding irradiated cells from immunized animals to normal cell populations. The degree of normal cell blastogenic suppression was dependent on the ratio of irradiated immune to normal cells present in the assay medium. Suppression of humoral responses was demonstrated in vivo. Immunized animals were incapable of producing antibody secreting cells to sheep red blood cells after an intraperitoneal inoculation of SRBC. Unimmunized animals produced a significant number of plaque forming cells as measured by a direct plaque forming cell assay. Lymphokine activity was not impaired in spleen cells from mice that exhibited other manifestations of suppression. Taken together, these data provide evidence to indicate that the induction of suppression may not correlate with increased pathogenesis, but rather be closely associated with protective immunity. Data also provide circumstantial evidence to indicate that lymphokine induction may be important in the development of protective immunity to C. psittaci in the mouse.
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PMID:Immunomodulation and Chlamydia: immunosuppression and the protective immune response to C. psittaci in mice. 305 73

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

In the present study, some basic effects of Eubacterium lentum (TYH-11), isolated from normal intestinal flora, upon the immune system and various experimental tumor cell lines were investigated. E. lentum showed no direct cytotoxicity against Ehrlich ascites tumor, while Serratia marcescens (TY-142) did show direct cytotoxicity. E. lentum presented striking antitumor activity which differed according to the injection route and time. This strain showed antitumor activity against 11 experimental tumor cell lines including Ehrlich ascites tumor, Meth-A, etc., but not against EL4 or Lewis lung carcinoma. The antitumor activity in this strain was recognized to lie in the cell wall and granular fractions. The effect of this strain on the immune system was studied by using plaque formation and the footpad reaction. When mice received 5 injections of E. lentum, the plaque number increased to treble the control level. Spleen weight was also increased following administration of E. lentum. In normal and tumor-bearing mice immunized with SRBC alone, the footpad reaction was increased significantly to the control level by administration of E. lentum.
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PMID:Antitumor activity and its properties of Eubacterium lentum. 312 99


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