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)

Spleen cells of (C57BL/6 X C3H/He)F1 mice were assayed for natural killer (NK) cell activity against YAC-1 and FBL-3 lymphoma targets at several intervals after total-body exposure to a high sublethal dose of 137Cs or 60Co gamma-rays. NK cell activity did not decline for the first 12 days but decreased sharply thereafter and remained low until day 24. The recovery of splenic NK cell activity was delayed. Beginning on day 28, the activity was slowly increased, reaching near-normal levels (80% of controls) 41-59 days after irradiation. Suppressor cells detectable during the period of lowest NK cell activity, i.e., on days 17 and 19, may have been responsible for the delayed and slow recovery. These studies indicated that a) mature effectors of natural cytotoxicity are relatively radioresistant renewable cells with a lifespan of about 2 weeks whose progenitors are radiosensitive cells b) the kinetics of decline and especially of recovery of NK cell activity may be influenced by suppressor cells. Should NK cell activity confer resistance to autochthonous lymphomas in vivo, it may be a significant consideration for strategies of tumor therapy by cytotoxic agents that reconstitution of the NK cell pool is a slow process and that suppressor cell function must be overcome for full recovery.
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PMID:Decline of natural killer cell activity in sublethally irradiated mice. 27 34

Killer helper factor (KHF) was previously found to be produced by a human T cell hybridoma, 24A . CA2. We studied the therapeutic effects of interleukin-2 (IL-2) and KHF on the inhibition of pulmonary metastases of syngeneic Lewis lung carcinoma (3LL) in C57BL/6N mice. Multiple subcutaneous (sc) injections of IL-2 plus KHF had significantly more effect than injections of IL-2 alone in inhibiting spontaneous pulmonary metastases and prolonging survival of the mice. The effect of KHF with IL-2 on induction of lymphokine (IL-2)-activated killer (LAK) activity against P-29 cells was examined in the murine system. Spleen cells generated LAK activity after incubation for 4 days with more than 500 U/ml of IL-2. In contrast, KHF alone did not render spleen cells cytotoxic. The combination of these lymphokines at subthreshold concentrations, however, resulted in significant in vitro induction of LAK activity. The LAK activity of splenocytes incubated with IL-2 plus KHF was maximal after 4 days, and persisted for longer than that of cells treated with IL-2 alone. The LAK cells induced by KHF plus IL-2 were also cytotoxic to FBL and YAC-1 cells. Moreover, spleen cells of mice bearing lung metastases could be induced to the cytotoxic state by sc injections of IL-2 plus KHF. These results indicate that combination treatment with IL-2 and the new lymphokine KHF should be useful clinically in inducing LAK activity for inhibition of pulmonary metastases.
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PMID:Enhancement of therapeutic effect of interleukin-2 on spontaneous pulmonary metastases of Lewis lung carcinoma by killer helper factor associated with increased induction of killer activity. 250 76

Although in vivo-primed cells are known to be rendered more effective in adoptive tumor therapy by secondary sensitization in vitro, they were tested only at the time of maximum in vitro cytolytic reactivity. Since the requirements for in vitro cytotoxicity and tumor therapy differ, the present study was designed to evaluate and compare the influence of culture duration on these two effector functions. Spleen cells from inbred C57BL/6 mice primed in vivo with the Friend virus-induced leukemia FBL-3 were secondarily sensitized in vitro by culture with tumor and tested for cytotoxicity in vitro in a 4-hour 51Cr release assay and for therapeutic efficacy in vivo against established tumor. In vivo-primed cells tested directly without prior culture were effective in therapy but were not cytotoxic in vitro. Culture of primed cells for 3 days rendered them cytotoxic as measured in vitro. This cytotoxicity increased through day 5, then it plateaued. Cultured duration modified the in vivo efficacy of primed cells differently. Cells cultured for 3 days with secondary sensitization by tumor became more effective in tumor therapy than noncultured primed cells. Increasing the duration of in vitro sensitization from 3 to 5 days did not enhance in vivo therapeutic efficacy, despite a concurrent increase in in vitro cytotoxicity. However, further lengthening of the culture duration to 7 days rendered cells more effective in vivo. These discrepancies presumably reflect different effector cell requirements and/or regulation operative for tumor lysis during a short-term in vitro assay and for tumor eradication following adoptive transfer of immune cells in vivo.
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PMID:Chemoimmunotherapy of a Friend leukemia with cells secondarily sensitized in vitro: effect of culture duration on therapeutic efficacy. 694 87

Spleen cells from C57BL/6 mice immunized in vivo with a syngeneic Friend virus-induced leukemia, FBL-3, were specifically activated by culture for 7 d with FBL-3, then nonspecifically induced to proliferate in vitro for 12 d by addition of supernatants from concanavalin A-stimulated lymphocytes containing interleukin 2 (IL-2). Such long-term cultured T lymphocytes have previously been shown to specifically lyse FBL-3 and to mediate specific adoptive therapy of advanced disseminated FBL-3 when used as an adjunct to cyclophosphamide (CY) in adoptive chemoimmunotherapy. Because the cultured cells are dependent upon IL-2 for proliferation and survival in vitro, their efficacy in vivo is potentially limited by the availability of endogenous IL-2. Thus, the aim of the current study was to determine whether exogenously administered purified IL-2 could augment the in vivo efficacy of long-term cultured T lymphocytes. Purified IL-2 alone or as an adjunct to CY as ineffective in tumor therapy. However, IL-2 was extremely effective in augmenting the efficacy of IL-2-dependent long-term cultured T lymphocytes in adoptive chemoimmunotherapy. The mechanism by which IL-2 functions in vivo is presumably by promoting in vivo growth and/or survival of adoptively transferred cells. This assumption was supported by the findings that IL-2 did not enhance the modest therapeutic efficacy of irradiated long-term cultured cells that were incapable of proliferating in the host and was ineffective in augmenting the in vivo efficacy of noncultured immune cells that are not immediately dependent upon exogenous IL-2 for survival.
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PMID:Augmentation of the anti-tumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2. 697 16

Resistance and/or susceptibility for Friend leukemia virus (FLV)-induced leukemogenesis was examined in the fully H-2 incompatible C57BL/6 (B6)-->C3H radiation bone marrow chimeras (RBMC). The results indicated that B6-->C3H chimeras never developed FLV-induced leukemias when infected with FLV 4 months after bone marrow transplantation (BMT). Spleen cells from B6-->C3H chimeras that were preimmunized with 100 Gy-irradiated FBL-3 cells (FLV-induced leukemic cell line originated from B6 mice) were shown to generate anti-FBL-3 specific T-cell proliferation as well as cytotoxic T cells. We also found that when bone marrow cells from B6 mice were mixed with those from C3H mice and then grafted into supralethally irradiated C3H mice, resulting chimeras whose peripheral blood contained less than 30% C3H-derived (susceptible) cells were refractory to FLV-induced leukemogenesis. On the other hand, when C3H mice were infected with FLV and then supralethally irradiated 5 days later and grafted with bone marrow from B6 donors, they developed leukemias which were of B6 origin. Athymic nu/nu mice of B6 background were again shown to develop leukemia following infection with FLV. Possible implication of these findings on the role of T cell-mediated immune response in resistance to FLV-induced leukemogenesis and the immunocompetent nature of fully H-2 incompatible RBMC were discussed.
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PMID:Friend leukemia virus-induced leukemogenesis in fully H-2 incompatible C57BL/6-->C3H radiation bone marrow chimeras. 832 Oct 19