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

It is generally accepted that T lymphocyte-mediated autoimmunity contributes to the pathogenesis of Type 1 diabetes in humans and animals. Using spleen cells from nonobese diabetic (NOD) mice, a model of human Type 1 diabetes, we have analyzed the subset of T lymphocytes by flow cytometry and investigated concanavalin A (Con A)-induced interleukin 2 (IL-2) production and cell proliferation. NOD mice showed a higher percentage of Thy1.2+, L3T4+, and Lyt2+ T lymphocytes than did control ICR mice through the whole age examined. Spleen cells from a large majority of NOD mice were found to generate very low IL-2 production and cell proliferation in response to Con A. However, a few mice preserved their responsiveness to Con A. The following reasons may indicate that macrophage-mediated suppression participates in the deficient function of NOD spleen cells. (a) Macrophage depletion from NOD spleen cells retrieved Con A-induced IL-2 production. (b) Thioglycollate-induced peritoneal exudate cells containing many activated macrophages could completely suppress cell proliferation. (c) Prostaglandin synthetase inhibitor indomethacin reversed the suppression of IL-2 production by macrophages. (d) Conversely, exogenous prostaglandins could show the partial suppression of IL-2 production. These results suggest that activated macrophages suppress the response of NOD spleen cells to Con A mostly through prostaglandins. This impairment may contribute to the pathogenesis of Type 1 diabetes in NOD mice.
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PMID:[Cellular immune dysfunction in the NOD mouse: suppression of concanavalin A-induced responses in spleen cells by activated macrophages]. 258 13

Spleen cells that are cultured with interleukin 2 for as short a time as 4 days develop the ability to lyse syngeneic natural killer-resistant tumor cells but not to lyse syngeneic lymphoblasts. When mice were subjected to partial hepatectomy (HEP), the spleen cells exhibited not only an augmentation of natural killer activity, but also an augmentation of in vitro induction of lymphokine activated killer (LAK) cells. Furthermore, the LAK cells exhibited lytic activities against syngeneic lectin-induced lymphoblasts and regenerating liver cells. The sensitivity of regenerating liver cells to lysis by LAK cells was detected as early as one day after HEP, and continued until day 14. Analysis by cell depletion techniques using monoclonal antibodies and complement, as well as discontinuous gradient sedimentation, indicated that the LAK cells activated by HEP were Thy-1+, Lyt-2+, asialo GM1+ and Lyt-1-, lymphocytes with a low density. After the intravenous (i.v.) administration of anti-asialo GM1 before HEP, the in vitro induction of LAK cells was remarkably inhibited.
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PMID:The augmentation of lymphokine-activated killer cells induced by partial hepatectomy in mice. 260 96

Spleen cells from non-obese diabetic mice were found to generate low interleukin 2 production and cell proliferation in response to concanavalin A. However, some of non-obese diabetic mice maintained in the same environment preserved their responsiveness to this T cell mitogen. Non-obese diabetic mice at every age had a higher percentage of Thyl.2, L3T4, and Lyt2-positive spleen cells than did control mice, suggesting that the dysfunction of spleen cells did not depend on the number of T cells or the ratio of these subpopulations. Evidence for macrophage-mediated suppression participating in the deficient function of splenic lymphocytes in this mouse model of insulin-dependent diabetes includes: 1) the restoration of mitogen-induced interleukin 2 production after the macrophages have been depleted by silica absorption form spleen cells; 2) the complete suppression of the cell proliferation by thioglycollate-stimulated peritoneal exudate cells from non-obese diabetic and control mice, and the partial suppression by spleen macrophages from non-obese diabetic mice; 3) the reversal of the suppression of interleukin 2 production by the prostaglandin synthetase inhibitor indomethacin (0.1-1 microgram/ml); 4) the partial suppression of interleukin 2 production, conversely, by the exogenous prostaglandins E1 and E2 (2.5 x 10(-6) mol/l). These results indicate that the activated macrophages existing among the spleen cells suppress the response of splenic T cells to concanavalin A. This impairment may contribute to the pathogenesis of insulin-dependent diabetes in non-obese diabetic mice.
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PMID:Suppression of concanavalin A-induced responses in splenic lymphocytes by activated macrophages in the non-obese diabetic mouse. 278 66

Spleen cells from mouse bone marrow chimaeras were cultured in vitro in mixed lymphocyte cultures (MLC) or in the presence of interleukin 2 (IL-2) without the added alloantigen. Precursors for the nonspecific cytotoxic cells (in this study: lymphokine-activated killer (LAK) cells) lysing natural killer (NK) cell-sensitive YAC-1 lymphoma could be found 10-12 days after the bone marrow reconstitution, simultaneously with the appearance of the NK activity. The ability of LAK cells to lyse NK-resistant tumour targets as well was demonstrated using the P 815 mastocytoma cell line; reactivity against this target was demonstrable 1 week later than the appearance on YAC-1 lysing cells. Phenotypically LAK cells derived from spleen cell cultures of bone marrow chimaeras did not differ from LAK cells derived from normal spleen cell cultures: precursors resided within the Thy 1-, asialo-GM1+ cell population, and effectors expressed both of these antigens. Splenic NK cells of early bone marrow chimaeras (up to 14-18 days after the bone marrow reconstitution) were Thy 1+ cells, and thus LAK cells of bone marrow chimaeras were not derived from these Thy 1+ NK cells. The treatment of effector cells with anti-Thy 1 antibody plus complement (C) abolished the lytic activity totally. However, these cells were not cytotoxic T cells, since alloreactivity, as an indication of the T-cell cytotoxicity, could not be demonstrated until 4-5 weeks after the bone marrow reconstitution.
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PMID:Lymphokine-activated killer cells in mouse bone marrow chimaeras. The relationship to natural killer cells and to alloreactive cytotoxic T cells. 286 99

A common prediction of clonal deletion/inactivation hypotheses is that cells with high avidity for tolerogen are preferentially eliminated, with low avidity cells being most likely to escape the tolerance induction mechanism. Thus it would be expected that the tolerogen-specific cells in tolerant mice would have a different repertoire than those in normal mice. To find evidence in favor of this prediction, neonatal B10.A mice were rendered tolerant to B10 by the injection of 15 X 10(6) (B10.A X B10)F1 spleen and bone marrow cells, and tolerance was assessed by the acceptance of B10 skin grafts for greater than 50 days. Mice rendered tolerant in this manner contain severely reduced (to less than 10% of normal) but detectable numbers of tolerogen-specific cytotoxic cell precursors that can be activated in the presence, but not absence, of exogenous interleukin 2. Spleen cells from the tolerant animals were compared with those of normal B10.A mice with respect to the expression of differentiation markers on the surface of B10-specific cytotoxic cells and their precursors, and the relative strength of the anti-B10 response toward Kb and Db as a measure of the repertoire of the cytotoxic cell populations. The T cell nature of the tolerogen-specific cytotoxic cells in both normal and tolerant mice was confirmed by their susceptibility to lysis by anti-Thy-1 or Lyt-2 antibody and complement. More importantly, cold target inhibition experiments showed that cytotoxic T cells from tolerant mice were inhibited to a greater degree by B10.A(2R) (KkDb) cold targets than B10.A(5R) (KbDd), suggesting that the response was preferentially directed at the D end of H-2, in direct contrast to normal B10.A spleen cells, which show a preferential response against Kb. Measurement of the frequency of anti-Kb and anti-Db cytotoxic T cell precursors in the spleens of normal and tolerant mice confirmed the differential specificities seen in the cold target experiments. The data suggest that neonatal tolerance induction results in repertoire modification of the anti-tolerogen response rather than a uniform decrease in anti-tolerogen reactivity. Possible mechanisms to explain the alteration in the repertoire of tolerant mice are discussed.
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PMID:Characterization of cytotoxic cells in mice rendered neonatally tolerant of MHC alloantigens: evidence for repertoire modification. 288 56

The present study was undertaken to define the cell populations which mediate lymphokine-activated killer (LAK) cell activity in mice. Because old mice exhibit markedly decreased to nondetectable natural killer (NK) cell activity, this age-associated change provided an advantageous system to examine the contribution of NK and T cells to LAK activity. Spleen cells from either young (6-9 weeks) or old (20-26 months) mice were cultured with 1000 units/ml of recombinant interleukin 2 (rIL 2) for 3-5 days. The cells were then tested in a 51 Cr-release assay for their cytotoxicity against NK-resistant fresh tumor cells (MCA-102). The LAK activity exhibited by spleen cells from old mice following 5 days of culture was equivalent to that developed by spleen cells of young mice. This result was contrary to what would be anticipated if mature NK cells comprise the primary precursors of LAK activity, and required further elucidation. The Thy-1 and asialo GM1 (ASGM1) phenotypes of LAK precursor and effector cells were therefore examined by depletion techniques using the appropriate antibodies plus complement. The results using spleen cells harvested after 5 days of culture with rIL 2 showed that LAK effector cells which developed from spleen cells of both young and old mice were predominantly Thy-1+ (85.3% young; 91.8% old) and some coexpressed ASGM1. Spleen cells were treated prior to culture to study the precursor cells. Development of LAK activity by spleen cells from both young and old mice was greatly reduced by pretreatment with anti-ASGM1 plus complement. However, since spleen cells of old mice exhibit very low mature NK activity, these data suggest that the LAK precursors, at least in old mice, may be ASGM1+ NK precursor cells rather than mature ASGM1+ NK effector cells. In addition, treatment with anti-Thy-1 plus complement inhibited generation of a significant proportion of LAK activity only in the spleens of old mice, suggesting a qualitative difference in LAK precursor cells with age and supporting the heterogeneity of the cells which are capable of developing LAK activity.
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PMID:Lymphokine-activated killer cells and aging in mice: significance for defining the precursor cell. 289 85

Suppressor activity was investigated in rats undergoing acute rejection of heterotopic cardiac allografts. Spleen cells were harvested at 7 days from LEW rats rejecting (LEW x BN)F1 heart grafts and fractionated into their T, T suppressor/cytotoxic, and T helper subpopulations. Transfer of alloimmune unseparated spleen cells to syngeneic recipients of (Lew x BN)F1 test grafts accelerated rejection from 8 to 6.5 days (P less than 0.01). Graft survival was prolonged to about 15 days (P less than 0.005) after transfer of the splenic T suppressor/cytotoxic fraction. Treatment of test graft recipients with ART-18, a mouse antirat monoclonal antibody directed against the rat interleukin 2 receptor on the surface of activated lymphocytes, increased graft survival to about 3 weeks (P less than 0.005), and to about 23 days (P less than 0.005) when test graft recipients were treated with ART 18 following transfer of alloimmune unseparated spleen cells. In contrast, ART-18 treatment of test graft recipients already injected with T suppressor/cytotoxic cells had no additive effect. Increased production of endogenous interleukin 2 occurred concomitantly with the onset of rejection in these animals; interleukin 2 release declined during the late stages of rejection when suppressor activity had increased. Similarly, in T-cell-depleted (B) rats, allograft rejection could be produced by immune reconstitution with sensitized lymphocytes, but could be significantly delayed by prior transfer of suppressor cells. These data document the presence of potent suppressor activity in the acutely rejecting host and suggest that the suppressor mechanisms are inhibited less than effector mechanisms by interleukin-2-receptor-targeted therapy.
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PMID:Development of suppressor lymphocytes during acute rejection of rat cardiac allografts and preservation of suppression by anti-IL-2-receptor monoclonal antibody. 294 63

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

Antigen-nonspecific suppressor T cells were identified in spleens of mice rendered unresponsive by sensitization of allogeneic antigen in combination with cyclosporine (CsA) treatment. Suppressor cells were obtained from C57BL/6 (B6, H-2b) mice treated with a single i.p. injection of 1 x 10(7) allogeneic P815 (H-2d) cells combined with a five-day course of CsA, a group that did not show any cytotoxic activity of spleen cells against P815 targets. These noncytolytic spleen cells displayed suppressor activity on the induction of cytotoxic T (Tc) cells of normal lymphocytes against not only P815 stimulator (80.9% suppression, P less than 0.01, responder:additional cell ratio = 2.5:1) but also third-party BW5147 (H-2k) stimulator (68.2% suppression, P less than 0.01). The unresponsive state appears to be due to suppressor T (Ts) cells that are nonadherent to plastic or nylon-wool, 1500 rads-sensitive, and Thy-1-positive. Capacities of spleen cells from CsA-P815-treated mice to release cytokines (interleukin 1 [IL-1]), interleukin 2 [IL-2], interleukin 3 [IL-3], and gamma-interferon [gamma-IFN]) were examined. Spleen cells from CsA-P815-treated B6 mice displayed 84.1%, 91.7% and 90.8% inhibition (0.35 +/- 0.07 U/ml, 1.4 +/- 0.29 U/ml, and 7.0 +/- 0.9 U/ml) of IL-1, IL-2, and gamma-IFN production compared with normal mice (2.2 +/- 0.54 U/ml, 16.9 +/- 2.1 U/ml, and 76.0 +/- 3.1 U/ml, P less than 0.01), respectively. However, IL-3 production was significantly less inhibition (46.1%, 2.35 +/- 1.0 U/ml in CsA-P815-treated mice and 4.36 +/- 1.7 U/ml in normal mice) compared with other cytokines (IL-1, IL-2, gamma-IFN). Two systems were employed to assess the immunosuppressive efficacy of antigen-nonspecific Ts cells in vivo. First, adoptive transfer (i.p.) of spleen cells harvested from CsA-P815-treated mice ten days after treatment on 3 consecutive days (days 0, 1, 2) at a 3 x 10(7) cell dose into virgin B6 mice that were immunized with P815 cells (1 x 10(7), day 0) completely inhibited the development of Tc cells against P815 targets (5% specific cytolysis, effector:target ratio [E:T] = 200). The suppressor effect was immunologically nonspecific; adoptive transfer of Ts cells from CsA-P815-treated mice also abrogated the development of Tc cells against third=party BW5147 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The in vivo immunosuppressive action of suppressor cells from alloantigen-cyclosporine-treated mice and the capacity of spleen cells to release interleukins and gamma-interferon. 296 48

Spleen cells (SC), splenic venous blood lymphocytes (SVL) and peripheral blood lymphocytes (PBL) from gastric and esophageal cancer patients were simultaneously tested for natural killer (NK) and nonspecific suppressor (Ts) cell activities. Furthermore, the influence of Ts activity on the augmentation of NK activity by a biological response modifier (BRM) was also investigated. Positive Ts activities were frequently detected in the SC, SVL and PBL of advanced cancer patients. The NK activities of SC and SVL were maintained even in advanced cancer patients, though significantly depressed NK activities were observed in the PBL of advanced cases. Cancer patient SC, SVL and PBL with positive Ts activity showed low NK activities. Moreover, the NK activities of SVL and PBL were low in the patients with positive Ts activity in SC. The NK activity of normal control PBL was strongly augmented by interleukin 2, interferon and OK-432. These BRMs exhibited comparable capacities to augment the NK activities of SC, SVL and PBL with negative Ts activity in cancer patients, however, the effects of these agents seemed to be low in cells with a positive Ts activity. These results suggested that NK activity might be regulated by nonspecific suppressor cells and the presence of suppressor cells might affect the augmentation of NK activity through BRM in circulating blood lymphocytes and also in spleen cells.
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PMID:The regulation of natural killer cell activity by splenic nonspecific suppressor cells and its modification in cancer patients. 297 25


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