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 analyzed the role of CD4+ and CD8+ T cells in H-2-disparate skin allograft rejection in the mutant mouse strain C.B-17/Icr scid with severe combined immunodeficiency. On the day of skin allografting, scid mice were adoptively transferred with negatively selected CD4+ or CD8+ splenocytes from normal unsensitized C.B-17/Icr mice. These populations were obtained using a double-mAb--plus--complement elimination protocol using anti-CD4 or anti-CD8 mAb that resulted in no detectable CD4+ or CD8+ cells by FACS and negligible numbers of cytolytic T lymphocytes by limiting dilution analysis in anti-CD8 treated populations. Spleen cells were removed from grafted mice at the time of rejection and were tested in vitro for antidonor reactivity in several assays: mixed lymphocyte culture, cell-mediated lympholysis, and LDA for CTL and for IL-2-producing HTL. The presence of Thy 1.2+, CD4+, or CD8+ cells was determined by FACS. All control C.B-17 mice and scid mice adoptively transferred with nondepleted CD4+, and CD8+ cells rejected skin allografts with similar mean survival times (15.6 +/- 1.5, 18.8 +/- 3.4, 18.0 +/- 5.4, respectively), whereas control scid mice retain skin allografts indefinitely (all greater than 100 days). C.B-17 syngeneic grafts survived indefinitely in all groups. At the time of rejection, splenocytes from scid mice receiving CD4+ cells had negligible donor-specific cytotoxicity in CML and negligible numbers of CTL by LDA, but demonstrated a good proliferative response in MLC and IL-2-producing cells by LDA (frequency = 1/1764). There were no detectable CD8+ cells present by FACS analysis. Conversely, splenocytes from scid mice adoptively transferred with CD8+ cells had strong donor-specific cytotoxicity in CML (58.8% +/- 16.1%) and CTL by LDA (frequency = 1/3448), but no significant proliferation was detected in MLC. There were no detectable CD4+ cells by FACS, but there were small numbers of IL-2-producing cells by LDA (frequency = 1/10,204). These data demonstrate that CD4+ cells adoptively transferred into scid mice are capable of mediating skin allograft rejection in the absence of any detectable CD8+ cells or significant functional cytolytic activity. The adoptive transfer of CD8+ cells also results in skin allograft rejection in the absence of detectable CD4+ cells. The detection of small numbers of IL-2 secreting cells in these mice may indicate that CD(8+)-mediated allograft rejection in this model is dependent on IL-2-secreting CD8+ cells.
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PMID:Mediation of skin allograft rejection in scid mice by CD4+ and CD8+ T cells. 135 12

Mice with severe combined immunodeficiency (SCID) were injected i.p. with 10 x 10(6) or 50 x 10(6) human leukocytes obtained from adult peripheral blood, umbilical cord blood, bone marrow and spleen from six group O individuals, together with allogeneic group A erythrocytes. Mice were bled every two weeks and levels of human IgG, IgM and anti-A were determined in the murine plasma. Spleen cells elicited the highest Ig levels (up to 5.2 mg/ml IgG) and umbilical cord the least (0-0.16 mg/ml IgG); maximum IgG levels were obtained at about 6-8 weeks after injection. Anti-A was detected in mice receiving adult peripheral blood or spleen leukocytes and immunizing erythrocytes 4-6 weeks after injection. Mice injected with the higher dose of leukocytes gave the best anti-A responses, but were more likely to develop tumours after 8 weeks.
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PMID:Specific anti-A responses of SCID mice populated with human lymphoid cells from peripheral blood, umbilical cord, bone marrow and spleen after immunization with group A erythrocytes [corrected]. 144 22

We describe the adoptive transfer of erosive arthritis to an immunodeficient host. Spleen cells from arthritic DBA/1 mice (H-2q), immunized 4-6 weeks previously with bovine type II collagen in adjuvant, were transferred intraperitoneally into SCID mice (H-2d). SCID recipient mice also received native or denatured type II collagen (100 micrograms intraperitoneally) at the time of cell transfer. Arthritis developed in five out of five mice approximately 2 weeks after injection of cells plus native collagen, whereas animals injected with cells plus denatured collagen did not show any clinical or histological evidence of arthritis. The minimum graft size required for successful transfer of arthritis was established at 10(7) DBA/1 spleen cells. Histological examination of the joints of arthritic SCID recipient mice revealed synovitis, fibrosis and erosion of cartilage and underlying bone. Mean circulating levels of anti-type II collagen IgG were found to be significantly higher in mice injected with native collagen than those injected with denatured collagen (40 micrograms/ml and less than 1 microgram/ml, respectively). The ability to transfer collagen-induced arthritis adoptively should facilitate the study of the cellular requirement and pathological mechanisms involved in the induction of this arthropathy.
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PMID:Successful transfer of collagen-induced arthritis to severe combined immunodeficient (SCID) mice. 160 30

We analyzed the T cell-independent production of IFN-gamma in the severe combined immunodeficiency (scid) mutant mouse. Spleen cells from scid mice secreted high levels of IFN-gamma in response to heat-killed Listeria monocytogenes (HKLM), but not to the T cell stimulus ConA. This response was ablated by prior removal of adherent macrophages. IFN-gamma secretion in vitro was preceded by the rapid production of TNF and was inhibited by addition of neutralizing mAb to TNF. Moreover, injection of scid mice with anti-TNF mAb increased the severity of infection with live Listeria and inhibited macrophage activation for class II-MHC expression. Finally, IFN-gamma secretion and class II-MHC expression were also inhibited by an antibody to asialoGM1, a reagent known to impair host NK cell function. These results suggest that TNF is a critical cytokine in the T cell-independent pathway of macrophage activation in scid mice.
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PMID:Tumor necrosis factor is involved in the T cell-independent pathway of macrophage activation in scid mice. 249 25

Spleen cells from C.B- 17 scid mice with severe combined immunodeficiency disease exhibit natural killer cell (NK) activity against YAC lymphoma targets in a standard 4-hr 51Cr release assay. The cytolytic activity is demonstrable only at high effector to target ratios but can be augmented at least sevenfold by the interferon inducer poly I:C. The pattern of target lysis is specific, because splenocytes from poly I:C-primed C.B-17 scid mice lyse NK-sensitive YAC cells and not the insensitive P815 mastocytoma. The presence of several NK-associated antigens on C.B-17 scid splenocytes was tested by pretreating cells with the appropriate antiserum plus complement before testing for NK activity. The results indicate that a proportion of NK effectors in C.B-17 scid mice bear surface NK 2.1 and Asialo GM1 but are negative for Thy-1.
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PMID:Natural killer (NK) cells are present in mice with severe combined immunodeficiency (scid). 398 96

Passive transfer of serum IgG or mononuclear cells from peripheral blood of a patient with paraneoplastic cerebellar degeneration (PCD) to rodents was carried out in order to examine the role of anti-Purkinje cell antibody (anti-Yo antibody) present in serum and cerebrospinal fluid of PCD patients. After a single injection of IgG into mouse brain, it was taken up by Purkinje cells and remained there for more than 36 h without Purkinje cell loss. Injection of PCD IgG together with complement or lipopolysaccharide-activated human macrophages or rat mononuclear cells into rat ventricles did not cause Purkinje cell loss. We also studied passive transfer of the PCD patient's lymphocytes to mice with severe combined immunodeficiency (SCID). We constructed a recombinant Yo fusion protein that has the leucine-zipper protein (Yo protein), the common epitope for anti-Yo antibody for immunizing mice, and that resulted in production of significant amounts of anti-Yo antibody. Spleen cells from these Yo protein immunized mice were injected intravenously or intracerebrally into naive mice that subsequently showed no neurological symptoms or loss of Purkinje cells. We conclude that the anti-Yo antibody, either in combination with or without complement or activated mononuclear cells, cannot be the sole cause of Purkinje cell loss.
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PMID:Trial to establish an animal model of paraneoplastic cerebellar degeneration with anti-Yo antibody. 2. Passive transfer of murine mononuclear cells activated with recombinant Yo protein to paraneoplastic cerebellar degeneration lymphocytes in severe combined immunodeficiency mice. 778 64

Previous studies of mice have implicated natural killer (NK) cells as mediators of protective activity against Toxoplasma gondii through their production of gamma interferon (IFN-gamma). In the present study, we have compared NK-cell activity in infected and uninfected SCID mice. Our data reveal that infection results in increased levels of IFN-gamma in serum and elevated NK-cell activity but that these NK cells were not cytotoxic for T. gondii-infected P815 cells. Treatment with anti-IFN-gamma antibody abrogated the increase in NK-cell activity and resulted in earlier mortality of infected mice. In vivo treatment with anti-asialo GM1 antiserum reduced NK cell activity and levels of IFN-gamma in serum but did not alter time to death. Spleen cells from infected mice produced higher levels of IFN-gamma than those from uninfected mice when stimulated in vitro with live T. gondii or parasite antigen preparations. Further analysis revealed that interleukin 10 (IL-10) inhibited, whereas tumor necrosis factor alpha (TNF-alpha) and IL-12 enhanced, IFN-gamma production by spleen cells from infected or uninfected mice. The combination of IL-12 and TNF-alpha induced higher levels of IFN-gamma from whole spleen cells of infected mice than from those of uninfected mice. Depletion of the adherent cell population from the spleen cells of infected mice led to a significant reduction in the levels of IFN-gamma produced after stimulation with IL-12 plus TNF-alpha. Similar results did not occur with cells from uninfected mice. These data indicate that other cytokines produced by the adherent cell population from infected mice may be involved in maximal production of IFN-gamma by NK cells stimulated with IL-12 and TNF-alpha. To assess the importance of endogenous IL-12, a polyclonal anti-IL-12 was administered to infected SCID mice. This treatment led to earlier mortality, indicating that endogenous IL-12 mediates resistance to T. gondii.
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PMID:Production of gamma interferon by natural killer cells from Toxoplasma gondii-infected SCID mice: regulation by interleukin-10, interleukin-12, and tumor necrosis factor alpha. 791 85

IFN-gamma is a cytokine known to play an important role in host defense against Salmonella typhimurium. The lymphoid cells required for in vitro production of IFN-gamma after S. typhimurium stimulation of mouse spleen cells was investigated. Spleen cells depleted of cells bearing NK1.1, asialo GM1, Thy 1.2, or CD5 resulted in a significant reduction in IFN-gamma production after stimulation with S. typhimurium. In contrast, Con A-induced IFN-gamma production was only slightly reduced after depletion of NK1.1- or asialo GM1-bearing cells. Spleen cells from SCID mice produced elevated levels of IFN-gamma after stimulation with S. typhimurium. IFN-gamma production by SCID spleen cells was dependent upon asialo GM1+ T cells, suggesting that NK cells were the cells producing IFN-gamma in response to S. typhimurium. Splenic adherent cells were required for optimal IFN-gamma production. However, direct contact between the adherent and nylon wool nonadherent (NWNA) cell populations was not essential. IFN-gamma production was observed when the adherent and NWNA cell populations were physically separated or when supernatant from S. typhimurium-stimulated adherent cells was added to NWNA cells. Optimal IFN-gamma production was dependent on the presence of TNF-alpha, inasmuch as addition of antibody to TNF-alpha to spleen cell or NWNA cell cultures significantly reduced IFN-gamma production. However, addition of rTNF-alpha did not induce IFN-gamma production by NWNA cells. These findings document the existence of a T-independent mechanism for early IFN-gamma production in response to S. typhimurium, and show that TNF-alpha is necessary but not sufficient for the production of IFN-gamma.
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PMID:Salmonella typhimurium induces IFN-gamma production in murine splenocytes. Role of natural killer cells and macrophages. 847 44

The cellular source of interleukin-6 (IL-6) during infection of mice with Listeria monocytogenes was investigated both in vitro and in vivo. Peritoneal cells taken at intervals from infected mice and cultured in vitro without added stimulus produced high titers of IL-6 peaking 2 days postinfection in a time course similar to that observed in vivo. Adherent cells with the morphology of macrophages were a major source of this IL-6. Spleen cells similarly harvested at intervals and cultured with heat-killed Listeria or heat-killed Brucella organisms as specific and nonspecific stimuli, respectively, showed two distinct IL-6 responses: (i) an early-phase response up to 5 days after infection when IL-6 production was elicited by either a specific or nonspecific stimulus, and when depletion of T cells had no effect, and (ii) a later response 7 to 10 days after infection when very high levels of IL-6 were produced in response to a specific stimulus. This response was lost when T cells were depleted in vitro or in vivo or in spleen cell cultures from mice with severe combined immunodeficiency. However, studies in vivo failed to show an important role for T cells governing serum IL-6. We conclude that most of IL-6 detected in vivo is produced by nonlymphocytes. Whether IL-6 produced by T lymphocytes in local foci of infection has any role in resolution of that infection is unknown.
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PMID:The cellular source of interleukin-6 during Listeria infection. 850 Sep

It has been reported that SCID (severe combined immunodeficiency, scid/scid) mice are more radiosensitive than normal mice. In the present studies, graded doses of radiation were given to bone marrow cells from SCID mice, and double-exponential survival curves were observed for day-9 and day-12 colony-forming units in the spleen (CFU-S). Single-exponential curves were found for SCID CFU in in vitro assays for granulocyte/macrophage-CFUs and erythroid burst-forming units, as reported elsewhere. Since the size of this more resistant fraction seems to decrease with stem-cell maturation, the finding implies that this fraction is a primitive subpopulation of the stem-cell compartment. The mean lethal dose (D0), however, of this less sensitive SCID CFU-S is much less than the D0 of regular CFU-S in normal littermates. Spleen colonies produced by SCID bone marrow were relatively small and abortive. The size of these colonies decreased nearly exponentially with increasing doses of radiation. These colonies were believed to be produced by this less sensitive fraction of the stem cells, which carried residual injuries. The colonies produced by the sensitive fraction have disappeared, being killed by a relatively low dose of radiation. This observation might account for the high lymphomagenesis arising from primitive hemopoietic stem cells in SCID mice, because the smallness of the colonies suggests that there is unrepaired or misrepaired damage. Furthermore, this less sensitive fraction might be a source of the "leaky" change of T and B cells, possibly due to the induction of an equivocal repair system which appears in the later stages of life in the SCID mice.
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PMID:Hemopoietic stem-cell compartment of the SCID mouse: double-exponential survival curve after gamma irradiation. 850 72


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