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)

Several aspects of T cell-mediated immune responses decline with age, but it is not known how gender affects this decline. Using 3- and 26-month-old male and female Fischer 344 rats, we examined the effects of sex and age on four different immune events that normally decline during aging: antibody synthesis to a T-dependent antigen, lectin-induced proliferative responses, IL-2 synthesis, and natural killer activity. We found that all these responses decreased with age. Spleen cells from aged females had higher spontaneous, phytohemagglutinin (PHA), and concanavalin A (Con A)-induced proliferative responses, and a two-fold increase in IL-2 synthesis than aged males, although no differences in these responses were evident between young males and females. Both natural killer (NK) activity and the ability to generate plaque-forming cells to sheep erythrocytes (SRBC) declined with age, but there were no differences between males and females for these responses in either age group. These data indicate that sex-associated differences in IL-2 synthesis and spontaneous and lectin-induced proliferative responses that are not detected in young animals become evident with advancing age.
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PMID:Sex differences in lectin-induced interleukin-2 synthesis in aging rats. 326 68

Spleen cells, obtained 2-5 days after in vivo priming with sheep erythrocytes (SRBC), were cultured to determine the presence of plaque-forming cell (PFC) precursors capable of developing into mature PFC under the influence of various stimulants. Lipopolysaccharide (LPS), added together with SRBC at the initiation of a 48-hr in vitro culture, enhanced the PFC response of primed spleen cells. In vivo priming for a minimum of 3 days was required, and maximal numbers of PFC were obtained from spleen cells primed for 4 days. Depletion of T lymphocytes from Day 3-primed spleen cells abrogated LPS-mediated enhancement, and addition of concanavalin A supernatants to the T-cell depleted system restored the enhancement, suggesting that LPS action required co-operation with a product(s) of activated T cells. Addition of various interleukin-2 preparations including recombinant human IL-2 to the system restored the LPS-mediated enhancement. The response of Day 3 cells from which T cells were eliminated as vigorously as possible was similarly restored by the addition of IL-2, LPS and antigen, suggesting that IL-2 reacts directly with PFC precursors that have developed IL-2 receptors. LPS-mediated enhancement, in the presence or absence of T cells, was also markedly dependent on the presence of SRBC during in vitro culture. These data suggest that, in co-operation with IL-2 and other co-factors, antigen plays a significant role in driving the later stages of differentiation and/or division of PFC precursors to mature PFC.
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PMID:Roles of IL-2 and antigen in the later stages of the primary antibody response. 331 78

Spleen cells from rats which had been hyperimmunized with mouse lymphokine-activated killer (LAK) cells, were fused with the mouse myeloma cell line, P3 X 63 Ag8.653. Antibodies secreted by 1500 cultures were selected by their blocking effect on LAK cell-mediated cytotoxicity in the absence of complement. Two monoclonal antibodies (KBA4 and KBA6) greatly inhibited the cytotoxic activity of LAK cells, which were induced from mouse spleen cells by culture with recombinant human interleukin 2 (r-IL-2). These antibodies also blocked the cytotoxic activity of natural killer (NK) cells, but activated macrophages (A-M phi) were only slightly sensitive to them. However, no effect of the antibodies on the cytotoxic activity of cytotoxic T lymphocytes (CTL) was detected. These data suggest that the specific antigen, lymphokine-activated cell-associated (LAA) antigen, defined by these monoclonal antibodies may be associated with the recognition mechanisms of broad-reactive killer (BRK) cell-mediated cytotoxicity. The observation that low levels of LAA antigen are distributed in all lymphoid cells and that it was significantly enhanced by treatment of the cells with r-IL-2 suggests that the antigen may be involved in lymphocyte-activation mechanisms. We also found that the LAA antigen consists of two distinct polypeptides with Mr of 180,000 and 95,000 Da, which are similar to that of LFA 1 antigen. However, the biological characteristics of LAA antigen did not coincide with those of LFA 1. Therefore, KBA MAb may recognize a carbohydrate epitope distinct from that of LFA 1.
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PMID:Lymphokine-activated cell-associated antigen involved in broad-reactive killer cell-mediated cytotoxicity. 387 1

Spleen cells from Lewis rats were cultured with 4 micrograms/ml Con A. These cells were then fused with BW 5147 mouse T lymphoma cells. Two hybrid clones (6B2-B8 and 6B2-E6) obtained by fusion formed CGF effectively. It was found that hybrid cells can be boosted to produce higher levels of CGF upon stimulation with Con A. 6B2-B8 express rat T cell markers. CGF formed by 6B2-B8 had a m.w. of 23,000 and 40,000. CGF was eluted from a Mono Q anion-exchange column with an FPLC system at 0.4 to 0.6 M NaCl as a major peak and at 0.8 M NaCl as a minor peak. CGF was eluted as three peaks with pH 4.1, 4.8, and 5.2 from a Mono P chromatofocusing column. CGF from 6B2-B8 does not contain IL-1, IL-2, IL-3, or CSF.
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PMID:Establishment of rat-mouse T cell hybridomas that constitutively produce a soluble factor that is needed for the generation of cytotoxic cells: biochemical and functional characterization. 387 81

Spleen cells derived from aged (30 mo) C57Bl/6 mice are shown to be deficient in the ability to generate suppressor cell activity in vitro. The addition of IL-2 to cultures containing aged cells restores this function to a large extent.
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PMID:Deficiency in suppressor T cell activity in aged animals. Reconstitution of this activity by interleukin 2. 622 39

Spleen cells from C57BL/6 beige mouse showed significantly lower cytotoxic T lymphocyte (CTL) generation in vitro against allogeneic target cells as compared with spleen cells from the wild type, whereas the heterozygous littermate showed a response similar to that of the wild type. In contrast, the responsiveness of beige spleen cells in the mixed lymphocyte reaction against allogeneic stimulator cells was in the normal range, suggesting that beige spleen cells recognize allogeneic stimulator cells to the same extent as spleen cells from normal mouse, resulting in a significant proliferation. The addition of interleukin 1 (IL-1)-containing supernatant from lipopolysaccharide-stimulated J774.1 cells to the culture of spleen cells from beige mouse stimulated with allogeneic cells restored the impaired CTL generation in a dose-dependent manner. The molecules responsible for restoration of the impaired CTL response co-migrated with IL-1 on gel filtration. The addition of purified interleukin 2(IL-2) also augmented the induction of CTL from beige spleen cells. However, the magnitude of augmentation by IL-2 was appreciably lower than that of augmentation by IL-1. These results suggest that the role of IL-1 in the induction of CTL is not only to provide a signal for activated amplifier T cells to release IL-2, but also to magnify otherwise low responsiveness of CTL-precursors and/or CTL-helpers. Moreover, intraperitoneal injection of IL-1 without allo-antigenic stimulation was able to restore the in vitro CTL responsitivity to allo-antigen but not the natural killer cell activity, indicating that IL-1 has a therapeutic potential in vivo for preferentially correcting impaired CTL generation associated with beige mutation.
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PMID:Interleukin-1 restores the impaired cytotoxic T lymphocyte generation in beige mutant mouse. 623 64

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

Spleen cells of BALB/c mice that had been inoculated with syngeneic plasmacytoma MOPC 104E were cultured for 11 days in T-cell growth factor (TCGF) and ultrasonicated tumor extract (USE). Cultured lymphocytes (MOPC-CL) possessed three-fold more lytic units than normal spleen cells cultured in TCGF without USE (N-CL). Moreover, the in vivo neutralization assay suggested that MOPC-CL were composed of at least two populations, one possessing tumor-specific and the other nonspecific antitumor activity. When 2 X 10(7) of MOPC-CL were administered IP to mice that had been inoculated IP with 10(5) MOPC 104E cells 5 days previously marginal prolongation of survival was observed. This effect was not augmented by the single injection of a larger number (5 X 10(7] of CL, but was augmented by the repeated daily administration for 4 days (from day 5 to day 8 after the inoculation) of the same total number (5 X 10(7] of CL. In addition, IP injection of the streptococcal preparation OK432 before the transfer of CL significantly enhanced the therapeutic efficacy, and resulted in a cure rate of 20%. The mechanism of this combined effect appears to involve the effect of OK432 on interleukin 2 (IL-2) regulation systems in vivo. Our culture system with TCGF and USE and our therapy system with OK432 and CL allow the clinical application of adoptive immunotherapy for the many types of solid cancers.
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PMID:Antitumor and therapeutic effects of spleen cells from tumor-bearing mice cultured with T cell growth factor and soluble tumor extract. 633 53

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

Splenic T lymphocytes of aged Lewis rats respond to Con A and PHA with diminished 3H-TdR uptake compared with splenic T lymphocytes of young Lewis rats. After immunization with allogeneic tumor cells, uptake of 3H-TdR in mixed lymphocyte-tumor cultures and T cell cytotoxicity against tumor target cells are significantly lower with spleen cells of aged rats compared with those of young rats. The culture of spleen cells of aged rats with Con A results in a diminished conversion of Ia-positive T cells from Ia-negative precursors compared with similar cultures of spleen cells of young rats. Spleen cells of both young and aged rats produce high amounts of IL-2 in response to Con A stimulation. "Old" T cells, however, bind relatively little IL-2, do not utilize it in culture, and do not respond to exogenous IL-2 with enhanced 3H-TdR uptake as do "young" T cells. In allogeneic MLTC, "old" T lymphocytes produce little IL-2 compared with "young" cells, and both "young" and "old" cells respond to exogenous IL-2 with enhanced 3H-TdR uptake and increased cytotoxic activity. The data suggest defects in the synthesis and/or recognition of IL-2 as well as defects in the regulation of Ia antigen expression may be responsible, in part, for the reduced T cell function in aged animals.
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PMID:T lymphocytes of young and aged rats. II. Functional defects and the role of interleukin-2. 645 82


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