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)

Natural suppressor (NS) cell activity is the ability of apparently unprimed "null" cells to nonspecifically suppress immune responses. Previously we have shown that NS cell activity from the spleens of mice undergoing chronic graft-vs-host disease (GVHD) is enhanced in vitro by activated T cell signals (e.g., Con A supernatant [CAS]). Here we asked if the naturally occurring suppressor activity found in the neonatal mouse spleen is caused by NS cells, and if so whether this NS activity is also responsive to T cell signals. Finally, we wanted to identify the material in the CAS to which the NS cells respond. Spleen cells from (BALB/c X B10.D2)F1 neonates contain potent, genetically unrestricted suppressor activity toward normal mitogen responses. The cells responsible for this suppression are nonadherent, Thy-, Ig- and are thus by definition NS cells. Neonatal spleen NS cells suppress the indicator Con A response of all mouse strains tested, but their behavior with regard to LPS responses is different. They significantly inhibit the indicator LPS response of allogeneic strains, but are less inhibitory of LPS-stimulated syngeneic (BALB/c X B10.D2)F1 and parental strains. However, the addition of CAS to these latter cultures enhances the NS inhibition of the LPS response to the level of suppression seen with a Con A response. Two lymphokines were able to replace the CAS. Recombinant interferon-gamma (rIFN-gamma) closely mimics the activity found with whole CAS, with low concentrations (1 U/well) being capable of enhancing the neonatal NS activity to near-maximal levels. Recombinant interleukin 2 (rIL 2) is also capable of stimulating the neonatal NS activity to near maximum. However, the rIL 2 must be added at much higher concentrations, taking greater than 50 U/well to get maximum activation of NS suppression. The addition of anti-IFN-gamma antiserum to these LPS suppression assays removes the ability of CAS to activate the neonatal NS cells. Anti-IFN-gamma antiserum also removes the ability of rIL 2 as well as rIFN-gamma to activate the NS cells. It thus appears that the rIL 2 is working by its ability to stimulate IFN-gamma production. Anti-IFN-gamma also removes the ability of the neonatal NS cells to suppress a Con A response. Therefore, it appears that neonatal splenic NS cells respond to, and are activated by, IFN-gamma to carry out their suppressive activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Natural suppressor (NS) activity from murine neonatal spleen is responsive to IFN-gamma. 295 98

Spleen cell blastogenesis to mitogens and antibody responses to sheep erythrocytes (sRBC) were tested in BALB/c mice with experimental E. cuniculi infections. Blastogenesis responses of spleen cells 1 week post-infection were significantly lower than normal to T-cell mitogens (Con A and PHA) and were unchanged in response to B-cell mitogens (LPS and PWM). After 2 weeks post-infection, the responses to T cell mitogens returned to normal. Mixing spleen cells from 1-week infected mice with cells from uninfected mice failed to reveal the presence of suppressor cells. Antibody responses to sRBC were significantly slower to develop in 1 week-infected mice compared with uninfected mice or mice infected 2 weeks earlier or at the same time as sRBC challenge. Infected mice displayed splenomegaly which was most pronounced 1 week post-infection and the differential spleen cell counts revealed the presence of lymphoblasts. Lymphohyperplasia appeared to cause the splenomegaly. No shifts in the proportion of Thy 1.2+ T cells, Ig+ B cells, or esterase-positive macrophages were detected. These results indicate that the immune system in BALB/c mice is depressed early during E. cuniculi infections.
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PMID:Modulated immune responsiveness associated with experimental Encephalitozoon cuniculi infection in BALB/c mice. 297 36

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

Spleen and peritoneal cells from unimmunized BALB/c mice were cultured in the presence of LPS for 24 hr and fused to produce hybridomas secreting antibodies against bromelain-treated mouse erythrocytes (BrMRBC). Three clones from spleen cells and eight clones from peritoneal cells were isolated and characterized further. All the monoclonal antibodies had IgMK isotype. Their reactivities against untreated and bromelain-treated erythrocytes from various species were assessed by hemolysis and indirect radioimmunoassay; all the clones had similar antigen specificities. On the isoelectric focussing patterns of light chains, they were separated into two groups, two and nine clones, and all the light chains in each group showed identical patterns. The two groups shared no common idiotope detectable by anti-idiotype antibodies prepared by immunization of rabbits with the monoclonal antibodies, but all the antibodies in each group shared common idiotopes. In each group, one antibody had a unique idiotope different from any other antibody, but eight antibodies in a group shared another identical idiotope. These findings suggest the restricted heterogeneity of anti-BrMRBC antibodies in the mouse.
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PMID:Mouse monoclonal antibodies against bromelain-treated mouse erythrocytes: reactivity with erythrocytes of various species of animals and idiotypes. 310 56

Mice infected with the protozoan parasite Trypanosoma cruzi are primed for the production of tumour necrosis factor/cachectin. Active infection is not required for stimulation of TNF production as formalin-fixed, but not heat-killed, parasites can act as a priming stimulus. Both epimastigote and trypomastigote stages of the parasite can prime for TNF production but on a per cell basis, trypomastigotes are more potent stimulators than epimastigotes and live parasites prime more efficiently than killed preparations. Although the priming effect of epimastigotes and trypomastigotes is dose-dependent when assayed 10 days after parasite injection, parasitemia levels in the infected mice do not correlate with the level of TNF production. Spleen cells from infected mice are also primed for the production in vitro of TNF in response to LPS or T. cruzi. These results suggest that TNF may be constitutively produced in vivo and that the priming for TNF production, or the production itself, may be regulated during the course of the infection in mice.
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PMID:Tumour necrosis factor (cachectin) production during experimental Chagas' disease. 314 Oct 92

In our laboratory, we have developed a murine model to examine GVHD across minor histocompatibility antigens. In our model, GVHD is induced by injecting B10.D2 spleen cells into irradiated BALB/c recipients. Seven to 10 days after irradiation and injection of cells, there are significant changes in cell function in the recipient spleens. In the B10.D2----BALB/c (600 rad) model, recipient spleen cells are profoundly unresponsive to Con A and LPS stimulation but show increased B cell activity measured by Staphylococcus aureus protein A plaque-forming activity. Spleen cells from such GVH mice profoundly suppress the mitogenic responses of normal BALB/c or B10.D2 spleen cells to Con A and LPS. The degree of impairment of the mitogenic response and the ability to suppress normal cells is proportional to the dose of cells used to induce GVH reactions. Both the inability to respond to mitogens and the capacity to suppress are also related to the dose of irradiation given to the recipients. In addition, immunosuppression across minor histocompatibility antigens shows an unevenhandedness. If we inject parental B10.D2 or BALB/c cells into F1 recipients (P----F1), there is greater inhibition of mitogenic responses when B10.D2 parental cells are given than when BALB/c cells are given to the irradiated F1 recipients. These experiments show that significant immunosuppression occurs during GVH reactions across minor histocompatibility barriers. The degree of suppression varies according to the dose of cells used to induce GVH, the dose of irradiation to the recipient and the "strength" of the GVH recognition system. Such experiments provide models for GVH disease seen in humans who receive treatment for leukemia or other diseases that involves recipient irradiation and infusion of HLA-identical bone marrow.
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PMID:Graft-vs-host reactions (GVHR) across minor murine histocompatibility barriers. I. Impairment of mitogen responses and suppressor phenomena. 315 67

We explored the immunoincompetence of mice undergoing a chronic graft-vs-host reaction (GVHR) across minor histocompatibility barriers. BALB/c and B10.D2 mice are H-2d and mls b, and differ only with regard to minor histocompatibility antigens (MiHA). A large number of BALB/c mice were unirradiated or were irradiated with 300, 600, or 900 R. They then were injected with 5 X 10(7) spleen cells from either allogeneic B10.D2 or syngeneic BALB/c mice. The spleen cells from these recipient mice were assayed at various times post-irradiation/injection for their proliferative response to Con A and LPS, their ability to suppress the mitogen responses of normal spleen cells, and for the genetic specificity of this suppression. Spleen cells from BALB/c mice that had received 600 or 900 R (but not 0 or 300 R), and allogeneic B10.D2 lymphocytes, became very hyporesponsive to mitogens and became suppressive in vitro by days 7 to 10 post-irradiation/injection. These phenomena persisted for the entire 49 days of the experiment. After an initial period of splenomegaly, the spleens of these mice gradually became depleted of viable lymphocytes. Initial characterization of suppressor cells found in the spleens of GVH mice showed that they were not removed by treatment with anti-Thy-1.2 plus complement. GVH suppressors also were not adherent to plates coated with antiserum directed towards murine Ig. In addition, these cells did not adhere to plastic plates. Thus, we believe that the suppressor cells found in mice undergoing GVHD across MiHA are not mature T cells, B cells, or macrophages, but belong to a class of suppressor cells termed natural suppressor (NS). Genetic analysis of NS cell activity showed that as early as 10 days post-irradiation/injection, NS cells inhibited mitogen responses of all mouse strains tested, the exception being the relative difficulty in suppressing the LPS response of B10.D2 (syngeneic with donor cells). By day 42, this had developed into an almost complete inability to suppress a B10.D2 LPS response, although at this time NS cells were still capable of inhibiting all the other mitogen responses of all strains tested, including the Con A response of B10.D2 spleen cells. Moderate amounts of mitogen unresponsiveness and suppressor activity were seen in the syngeneic groups (BALB/c----BALB/c) but only if recipients received 600 or 900 R. This was a transient phenomenon that was maximal at day 14, and which we believe to be a similar but less severe degree of immunoincompetence when compared with that seen with allogeneic stimulation in the B10.D2----BALB/c GVH model.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Graft-vs-host reactions (GVHR) across minor murine histocompatibility barriers. II. Development of natural suppressor cell activity. 316 Jul 74

We have been studying the mitogen hyporesponsiveness and immunosuppression induced in chronic murine graft-vs.-host disease (GVHD) induced across minor histocompatibility (MiHA) barriers. In this system, donor and recipient mice are major histocompatibility complex- and mls-identical, and are nonreactive in primary mixed leukocyte reactions. Spleen cells from B10.D2 (H-2d, mls b) mice were injected into irradiated (600 rad) BALB/c (H-2d, mls b) recipients. Recipient spleen cells are hyporesponsive to mitogens, and contain natural suppressor (NS) cells. We investigated the cellular requirements for both the in vivo induction and the in vitro expression of this GVH suppression. T cells are required in the graft, but they are not sufficient to induce suppression, and a non-T cell population is also required for maximum induction in vivo. T cells are also required for the maximum expression of NS cell suppressive ability in vitro. Early in the course of GVH, the suppressor cells are able to suppress the Con A and LPS response of all mouse strains tested (except for the relative difficulty in suppressing the B10.D2 LPS response). Later, they become almost completely unable to suppress the B10.D2 LPS response; while still being able to suppress the Con A and LPS response of all other strains tested (including the B10.D2 Con A response). This inability to suppress a B10.D2 LPS response can be brought back to almost complete suppression by the addition of concanavalin A supernatant (CAS). We present a hypothesis to explain what may be a common mechanism for GVH-induced suppression, total lymphoid irradiation-induced suppression, and neonatal tolerance. These situations all include rapidly proliferating lymphohematopoietic stem cell populations, and also have large numbers of NS cells. NS cells can suppress proliferating lymphoid populations, and their development and activity are greatly enhanced by T cell signals such as are supplied by donor T cells in chronic GVHD. Thus, NS cells may feed back on and downregulate self-reactive T cells or T cells responding to introduced foreign antigens.
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PMID:Synergism between T and non-T cells in the in vivo induction and in vitro expression of graft-vs.-host disease-induced natural suppressor cells. 316 77

Spleen cells from MRL-lpr/lpr, CBA and BALB/c mice were cultured in vitro and assayed for production of anti-nuclear antibodies. Spleen cells from all species produced IgM antibodies to a nRNP (U1-RNP)-specific antigen and to double-stranded DNA (dsDNA) after stimulation with LPS. The specificity of the anti-nRNP antibodies was shown, by immunoblotting, to be directed against the 33,000 MW polypeptide of nRNP/Sm. CBA mice produced more IgM autoantibody in vitro than MRL/lpr or BALB/c mice. In contrast, IgG anti-nRNP and anti-dsDNA antibody were not produced by any of the strains. Our data show that anti-nRNP and anti-dsDNA precursor B cells are part of the normal murine immune repertoire and are not confined to the MRL/lpr strain. This suggests that the spontaneous development of anti-nRNP and anti-dsDNA antibodies associated with systemic lupus erythematosis (SLE) is dependent on clonal stimulation and removal of suppressive influences.
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PMID:Anti-nRNP anti-nuclear antibody-secreting cells are represented in the B-lymphocyte repertoire of normal and MRL/MP-lpr/lpr lupus mice. 325 71

The lymphocyte composition of spleen, lymph nodes, bone marrow, and thymus of mice submitted to hydroxyurea treatments for four consecutive days was studied. The treatment selects for small lymphocyte populations that represent between 4 and 20% of control numbers in the various organs. Spleen and bone marrow contain the same B cell population with a low IgM, high IgD, low I-E phenotype, which respond to LPS at control clonal frequencies. The T cell compartment is equally depleted, and the lymphocytes remaining contain frequencies of clonable cells in response to mitogens and IL-2 that are comparable to those detected in normal spleen cells. Overall, the results suggest that only a minor fraction of all lymphocytes in a normal young adult mouse have life spans longer than 4 days.
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PMID:A phenotypic and functional analysis of long-lived B and T lymphocytes. 326 12


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