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)

Prior work has shown that purified, resident, and inflammatory peritoneal macrophages are weak stimulators of the allogeneic MLR. We have identified conditions whereby thioglycollate-elicited macrophages become stimulatory, but primarily for the CD8+ T cell subset. The conditions were to treat the macrophages with neuraminidase and to supplement the MLR with rIL-2. These treatments together led to proliferative and cytotoxic responses by isolated CD8+ but not CD4+ T cells. Likewise when MHC-congenic strains were evaluated, an MLR was observed across isolated class I but not class II MHC barriers. Pretreatment of the macrophages with IFN-gamma further enhanced expression of class I MHC products and stimulatory activity, but did not seem essential. While these treatments did not render macrophages stimulatory for an MLR in purified CD4+ cells, blastogenesis of CD4+ cells was observed when the MLR involved bulk T cells. Small allogeneic B lymphocytes behaved similarly to macrophages, in the pretreatment with neuraminidase and supplementation with rIL-2 rendered B cells stimulatory for allogeneic, enriched, CD8+, but not CD4+, T cells. Spleen adherent cells, which are mixtures of macrophages and dendritic cells, stimulated both CD4+ and CD8+ T cells, and neither neuraminidase nor exogenous IL-2 was required. We think that these data suggest that most macrophages and small B cells lack three important functions of dendritic cells: a T cell-binding function that can be remedied by neuraminidase treatment, a T cell growth factor-inducing function that can be bypassed with exogenous IL-2, and an IL-2 responsiveness function that is required by CD4+ lymphocytes.
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PMID:Neuraminidase-treated macrophages stimulate allogenic CD8+ T cells in the presence of exogenous interleukin 2. 326 11

T cell growth is principally regulated by the lymphokine interleukin 2 (IL 2). Following induction of IL 2 receptors, immunologically normal cells proliferate and will continue to do so until the level of IL2 becomes limiting. Spleen cells from autoimmune-prone mice and peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE), however, are severely deficient in their capacity to both produce and respond to IL 2 following a challenge with mitogenic lectins. These observations have suggested the possibility that IL 2 may not function as a T cell growth factor in the autoimmune milieu. In order to determine the requirements for T lymphocyte proliferation in autoimmunity, MRL-lpr/lpr mice were studied. Spleen cells from this murine model of lupus exhibit profound defects in IL 2 activity in vitro. Yet, paradoxically, massive expansion of the T cell pool occurs in vivo. While spleen cells from such mice were, indeed, unable to produce IL 2 or to proliferate when stimulated with concanavalin A (Con A), the combination of Con A plus the comitogen phorbol myristate acetate (PMA) engendered substantial IL 2 production and normal cellular proliferation. Since numerous lymphokines are produced when cells are cultured with Con A + PMA, it remained to be shown that IL 2 was, in fact, the responsible growth factor. We found that culturing lpr spleen cells with an anti-IL 2 receptor antibody abrogated the mitogenicity of Con A + PMA; that on stimulation with Con A + PMA, MRL-lpr/lpr T cells expressed IL 2 receptors, and that addition of recombinant IL 2 to the receptor positive population resulted in marked proliferation. Furthermore, by two-color flow cytometric analysis it was demonstrated that T cells which bear the phenotype of those which undergo clonal expansion in the lpr were capable of expressing IL 2 receptors. Thus, IL 2 can be utilized as a growth factor, in vitro, by autoimmune as well as normal T cells. The etiology of the Con A unresponsiveness of MRL-lpr/lpr cells remained to be clarified. We observed that, in contrast to the refractoriness of fresh cells, lymph node cells which had been cultured for several days in the absence of antigenic stimulation were capable of expressing IL 2 receptors and of proliferating on exposure to Con A. Using flow cytometry it was found that selective expansion of a subset of phenotypically "normal" lymphocytes had not occurred.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Signals required for activation and growth of autoimmune T lymphocytes. 608 44

Total lymphoid irradiation (TLI) was administered to (BALB/c X C57BL/6)F1 mice in eight daily doses of 200 rad (total 1600 rad). Spleen cells isolated from mice after treatment with TLI do not respond to alloantigens in vitro in a one-way mixed lymphocyte reaction (MLR), but normal reactivity recovers after approximately 2 mo. Radioresistant, antigen-nonspecific suppressor cells are documented in the spleens of TLI-treated mice immediately after radiotherapy, but suppressive capacity gradually disappears within 30 days. After TLI, the spleen is repopulated with large cells, the proportion of which is greatest at a time when theta-bearing cells are still depleted. Radioresistant suppression is mediated predominantly by the large cell subset and is thymus independent. Suppressor function can be abolished by lethal physicochemical procedures including formaldehyde fixation, multiple freeze-thawing, and heating to 56 degrees C, and it cannot be conferred by supernatants of TLI-suppressed MLR suspensions. Suppression cannot be overcome by adding various cell factors including T cell growth factor (TCGF) and lymphocyte-activating factor (LAF), nor is it affected by a prostaglandin inhibitor. Equally potent radioresistant suppressive activity is documented by co-culturing cells derived from other sources enriched in large, immature hematopoietic cells, including fetal liver cells and bone marrow cells obtained from normal and congenitally athymic mice. The presence of a large cell population and MLR suppressor function is also documented in the spleens of mice treated with single dose or fractionated doses of lethal whole body irradiation, followed by reconstitution with bone marrow cells obtained from normal mice. The data suggest that MLR suppressor cells, which are large, immature and predominantly radioresistant, can be induced after a short and well-tolerated TLI regimen.
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PMID:Suppression of cell-mediated immune responses after total lymphoid irradiation (TLI). I. Characterization of suppressor cells of the mixed lymphocyte reaction. 614 Feb 88

We have reported that immunization of H-2k mice with lymphoid cells from various allogeneic strains induced a population of cells that could eliminate first-passage spontaneous AKR leukemia from the spleens of immuno-suppressed AKR (H-2k) hosts. In the present study, we examined the nature of the cells responsible for this graft-vs-leukemia (GVL) reaction and compared them to cytolytic cells detected in vitro. Spleen cells from alloimmunized CBA/J (H-2k) mice were selectively depleted of various subpopulations by treatment with antibody and complement (C), then tested in vivo for GVL reactivity. Cell suspensions depleted of Thy-1.2+, Lyt-1+, or Lyt-2+ lymphocytes had no significant GVL reactivity, whereas suspensions depleted of NK-1.2+ cells retained GVL reactivity. The GVL-reactive cells persisted in H-2-compatible donor mice for up to 56 days. Lyt-1+2+ lymphocytes that were cytotoxic for cultured AKR leukemia cells in vitro could be detected in the spleens of alloimmunized H-2-compatible mice after expansion of the cells in T cell growth factor. Using quantitative limiting dilution cytotoxicity assays, we found that the frequency of leukemia-reactive cytotoxic lymphocytes (CL) in the spleen showed a direct correlation with the GVL efficacy of the cells in vivo. Alloimmunization was essential for induction of the GVL-reactive cell population. CL in alloimmunized mice consisted of heterogeneous cytotoxic specificities; i.e., some CL were leukemia-specific, others lysed only nonleukemic AKR target cells, and a third group mediated killing of both leukemic and nonleukemic target cells. The CL appeared to be H-2 restricted and specific for non-H-2 antigens shared by the AKR leukemia and the alloimmunizing cells.
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PMID:Characterization of alloimmunization-induced T lymphocytes reactive against AKR leukemia in vitro and correlation with graft-vs-leukemia activity in vivo. 619 24

The immunologic potential of T lymphocytes and antigen-presenting cells (APC) from male and female mice were compared. Lymphocytes from female mice or from male mice that cannot produce and respond to testosterone (Tfm/y) were more reactive than male lymphocytes to alloantigens in MLR. Spleen cells from Tfm/y mice equipped with estrogen implants showed a higher responsiveness than control Tfm/y to alloantigens. The removal of suppressive adherent cells or the addition of T cell growth factor (TCGF) enhanced the proliferative activity of the cells in the MLR. The responsiveness of female cells to alloantigens, however, remained superior to that observed in male cells. Similarly, in the presence of TCGF, thymocytes from female mice react more effectively than male cells in MLR. In addition, Con A-stimulated spleen cells from female mice produce more interleukin 2 (IL 2) than do spleen cells from males or female mice treated with testosterone. Lymphocytes from immunized mice were tested for their ability to respond to soluble antigens (KLH and OVA) in vitro. Again, female immunocompetent cells respond more vigorously than male cells or cells originating in female mice with testosterone implants. APC from female spleen were more efficient than male APC in initiating a secondary response in primed lymphocytes from either males or female mice. Moreover, castration of male mice enhanced, and treatment of female mice with androgen reduced, the efficiency of antigen presentation. In conclusion, these data suggest that female cells are superior to male cells in immunologic functions that are known to be associated with reactions to and recognition of histocompatibility antigens, i.e., antigen presentation and MLR. Furthermore, our present data indicate that the differential reactivity of immunocytes between male and female mice depends on the hormonal balance of the animal.
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PMID:Sex-associated differences in the regulation of immune responses controlled by the MHC of the mouse. 622 95

The present study was designed to examine the cellular requirements for the generation of the suppressor T cells induced in the presence of fetal calf serum in culture. When C57Bl/6 mouse spleen cells were cultured for 4-5 days, these precultured cells were shown in mixing experiments to suppress the generation of cytotoxic effector cells (CTL) against allogeneic P815 cells or the generation of anti-SRBC humoral response by freshly explanted C57Bl/6 spleen cells. Spleen cells cultured in the presence of silica (0.5 mg) for 4 days, did not develop suppressor activity. However, when silica was added 3 days after the start of the suppressor generation culture, the development of suppressor cells was only slightly affected, although the phagocytic activity of these spleen cells was still totally abolished. When plastic or G-10 Sephadex column nonadherent spleen cells were cultured alone for 4-5 days, these cells did not suppress the generation of CTL or anti-SRBC humoral response. When the nonadherent spleen cells were cultured with plastic adherent spleen cells, however, suppressor cells developed and the suppressor activity of these cells was dependent on the number of adherent spleen cells co-cultured with the non-adherent spleen cells. This activity of the adherent spleen cells was insensitive to treatment with anti-Thy 1.2 serum plus complement and to X-irradiation. Furthermore, adherent PEC could not substitute for adherent spleen cells, indicating a possible tissue specificity for the macrophages in the adherent cell fraction which can function in supporting and/or accelerating the differentiation of "immature" suppressor T cells. Finally, culture-induced suppressor T cells were sensitive to X-irradiation and their activity was refractory to IL2 (TCGF), whereas the activity of alloantigen-induced suppressor cells was sensitive to IL2.
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PMID:Induction of suppressor T cells in culture--I. Cell-cell interactions. 623 13

Lewis rats injected in the hind paw with Mycobacterium butyricum develop a severe polyarthritis which shares certain features in common with rheumatoid arthritis in man. Spleen and peripheral blood mononuclear cells from rats with this form of arthritic disease proliferate poorly in vitro in response to concanavalin A (con A), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM). The splenic hyporesponsiveness appears within four days of M. butyricum injection (three to five days prior to the development of detectable arthritis), reaches a peak 16-22 days following injection, and persists for at least 40 days. Buffalo strain rats injected with M. butyricum do not develop arthritis, and their spleen cells respond normally to con A, PHA, and PWM. In response to lipopolysaccharide (LPS) the synthesis of interleukin 1 (IL-1) by spleen or peritoneal macrophages from arthritic Lewis rats equalled or exceeded that of macrophages from normal rats. In contrast splenic T cells from arthritic rats produced reduced amounts of interleukin 2 (IL-2; T cell growth factor) in response to stimulation with PHA or con A. Moreover, con-A-activated spleen cells from arthritic rats failed to bind IL-2 and to respond to this growth factor with increased 3H-TdR uptake as did normal spleen cells. In-vitro treatment of 'arthritic' cells with 10(-5) M indomethacin did not restore to normal their reduced mitogen responsiveness, and spleen cells from normal and arthritic rats were equally sensitive to the inhibitory effects of prostaglandin E2 on con-A-induced proliferative responses. These results indicate that peripheral lymphoid function is compromised in rats with adjuvant-induced arthritis and that this functional deficit is mediated by aberrant synthesis of and response to IL-2 by T cells of arthritic animals.
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PMID:Lymphoid abnormalities in rats with adjuvant-induced arthritis. I. Mitogen responsiveness and lymphokine synthesis. 633 88

Supernatants from Con A-stimulated rat spleen cell cultures containing TCGF were able to increase the sensitivity of the microcytotoxicity assay. Spleen cells from mice immunized with irradiated syngeneic tumour were precultivated for 24 h in a TCGF-containing medium. The precultivated immune spleen cells, when allowed to react with syngeneic tumour target cells, displayed a higher cytotoxic effect than the same immune spleen cells precultivated in a medium without TCGF. Similarly, the addition of TCGF-containing medium to the effector cells during the microcytotoxicity assay increased the cytotoxic effect. Combination of both schedules, i.e., precultivation of the immune effector cells in a TCGF-containing medium and addition of TCGF-containing medium to the effector cells during the microcytotoxicity assay produced the highest increase in sensitivity of the microcytotoxicity assay.
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PMID:Increase in sensitivity of the microcytotoxicity assay by T cell growth factor (IL-2)-containing preparations. 660 90

We have previously shown that following oral administration of myelin basic protein (MBP), regulatory T cells are generated from gut-associated lymphoid tissue and that these cells suppress experimental allergic encephalomyelitis (EAE). These regulatory T cells produce transforming growth factor-beta (TGF-beta) with various amounts of IL-4 and IL-10 and these TGF-beta-secreting T cells have been termed Th3 cells. T cells in lymphoid organs drained by mucosal sites secrete IL-4 as a primary T cell growth factor. In the present study, we examined the role of IL-4 on oral tolerance and in the generation of TGF-beta secreting cells. Treatment of (PLJ x SJL)F1 mice with intraperitoneal (i. p.) IL-4 and low-dose oral MBP (0.5 mg) given three times reduced the severity of EAE, whereas i.p. injection of IL-4 alone or oral MBP alone given in these suboptimal doses, showed no protection. Spleen cells from protected mice produced increased amounts of TGF-beta and reduced IFN-gamma upon stimulation with MBP in vitro. Mucosal MBP-specific IgA production was significantly increased in IL-4 plus MBP fed animals. Moreover, oral administration of IL-4 (1 microg per feeding) also enhanced the suppression of EAE by oral MBP and this protective effect was reversed by administration of anti-TGF-beta antibody in vivo. Reverse transcription-PCR showed enhanced suppression of IFN-gamma in Peyer's patch in animals fed MBP and IL-4 versus those fed MBP alone. We then investigated the role of IL-4 in the generation of TGF-beta-secreting cells using MBP Ac1-11 TCR transgenic animals. Cells were cultured with IL-2, IL-4, or IFN-gamma in the presence of MBP and limiting dilution analysis for cytokine-secreting cells performed. We found that IL-4, but not IL-2 or IFN-gamma, generated TGF-beta-secreting T cells from naive splenic T cells and that these cells provided help for IgA production. These findings demonstrate that IL-4 is a differentiation factor for TGF-beta-secreting Th3 cells and oral IL-4 has a synergistic effect on low-dose oral tolerance that is associated with increased TGF-beta secretion.
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PMID:IL-4 is a differentiation factor for transforming growth factor-beta secreting Th3 cells and oral administration of IL-4 enhances oral tolerance in experimental allergic encephalomyelitis. 975 65