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PubMed2004

The origin of biliary ductular cells that appear in the spleen after transplantation of hepatocytes.

Transplantation of rat hepatocytes into the syngeneic rat spleen results in the appearance of cytokeration (CK)-19-positive biliary cells that form ductules. The exact origin of CK-19-positive cells is not known and the possibility that they are derived from biliary cells or precursors of oval cells in transplanted hepatocyte preparations has been raised. In the present study, we found that the number of CK-19-positive biliary cells increased rapidly after transplantation of hepatocytes, reached the maximum at 4 weeks, and then gradually decreased. However, a Ki-67 labeling index of CK-19-positive biliary cells was low and showed no significant changes throughout the experimental period. In addition, no or few CK-19-positive cells appeared in the spleen after transplantation of nonparenchymal liver cells enriched with biliary cells. These results showed that biliary cells were not the source of CK-19-positive cells in the spleen. Impairment of precursors of oval cells in the liver by administration of 4,4'-diaminodiphenylmethane 24 h before transplantation of hepatocytes did not prevent the appearance of CK-19-positive biliary cells in the spleen. Moreover, transplantation of nonparenchymal cells carrying an increased number of oval cells by means of treatment with 2-acetylaminofluorene and partial hepatectomy resulted in no appearance of CK-19-positive biliary cells in the spleen. These results ruled out oval cells as the origin of CK-19-positive biliary cells in the spleen. Because CK-19-positive biliary cells appeared in the spleen only when hepatocyte fractions were transplanted, we suggest transdifferentiation of heptocytes may be the mechanism by which CK-19-positive biliary cells are generated.

Animals↗
PubMed2002

Spleen is a primary site for activation of platelet-reactive T and B cells in patients with immune thrombocytopenic purpura.

We have recently reported that in patients with chronic immune thrombocytopenic purpura (IMTP), circulating T and B cells that are responsive to gpIIb-IIIa can induce anti-platelet autoantibody production. In this study, the frequencies and activation status of gpIIb-IIIa-reactive T and B cells were evaluated in the peripheral blood and spleen obtained from nine IMTP patients undergoing splenectomy. There was no difference in gpIIb-IIIa-reactive T cell frequencies between peripheral blood and spleen (6.4 +/- 2.6 vs 5.2 +/- 2.4 per 10(5) T cells), as determined by limiting dilution analysis, but activated T cells responsive to gpIIb-IIIa showing accelerated proliferation kinetics and those expressing CD154 were more frequent in spleen than in peripheral blood. The frequencies of anti-gpIIb-IIIa Ab-producing B cells, as determined by ELISPOT assay, were also similar in peripheral blood and spleen (61.2 +/- 24.0 vs. 77.7 +/- 45.3 per 10(5) B cells); however, an anti-gpIIb-IIIa Ab was spontaneously produced by splenocytes in vitro, but scarcely secreted by PBMCs. CD19(-)/surface Ig(-)/CD38(+)/CD138(+) plasma cells secreting anti-gpIIb-IIIa Ab were exclusively detected in the spleen. In serial analysis, the frequencies of circulating gpIIb-IIIa-reactive T and B cells were markedly decreased after splenectomy in patients with a complete response, but were unchanged in nonresponders. These findings indicate that an interaction between gpIIb-IIIa-reactive T and B cells inducing anti-platelet Ab production in IMTP patients occurs primarily in the spleen and that the significant number of gpIIb-IIIa-reactive T and B cells activated in the spleen are released into the circulation as memory cells.

Adult↗
PubMed2001

Role of Doppler sonography in the evaluation of accessory spleens after splenectomy.

OBJECTIVE: Splenectomy influences the Doppler blood flow pattern in the splenic artery. Blood flow in this vessel might return to normal if an accessory spleen increases in size after splenectomy. Our objective was to evaluate the resistive index of the splenic artery depending on the presence or absence of a hypertrophic accessory spleen in splenectomized patients. METHODS: The resistive index of the splenic artery was evaluated by duplex Doppler sonography in 19 splenectomized patients (8 with a hypertrophic accessory spleen) and in 8 healthy volunteers. The resistive index was measured within 3 cm of the origin of the splenic artery, and 3 different measurements were averaged. The presence or absence of a hypertrophic accessory spleen was diagnosed on the basis of sonography, computed tomography, magnetic resonance imaging, or scintigraphy, as well as by the presence or absence of Howell-Jolly bodies on a peripheral blood smear. RESULTS: The resistive index of the splenic artery in the splenectomized patients without a hypertrophic accessory spleen (mean +/- SD, 0.82 +/- 0.06; n = 11) was significantly (P < or = .0001) higher than in splenectomized patients with a hypertrophic accessory spleen (0.63 +/- 0.06; n = 8) and in control subjects (0.63 +/- 0.05; n = 8). CONCLUSIONS: In the splenectomized patient, a hypertrophic accessory spleen is associated with a normal resistive index in the splenic artery.

Adult↗
PubMed2000

Interleukin 18 induces a synergistic enhancement of interferon gamma production in mixed murine spleen cell-tumor cell cultures: role of endogenous interleukin 12.

Interleukin 18 (IL-18) reportedly synergizes with IL-12 and IL-10 for interferon gamma (IFN-gamma) synthesis and natural killer (NK) cell activity, respectively. Here we show that IL-18 alone induces low level IFN-gamma production by unstimulated Balb/c mouse spleen cells, but production is enhanced synergistically in cocultures of spleen cells and allogeneic living or fixed Yac-1 cells. Spleen cells could be primed with IL-18 prior to coculture with Yac-1 cells for IFN-gamma production, which also was observed in cocultures containing either syngeneic or xenogeneic tumor cells. IFN-gamma production in stimulated cocultures was abrogated almost completely by anti-IL-12 antibody and was unrelated to spleen cell lytic activity. IL-10 moderately inhibited IFN-gamma production induced by IL-18. Therefore, in spleen cell and tumor cell cocultures exposed to IL-18, high levels of IFN-gamma are produced by the spleen cells arising from a synergistic interaction between the exogenous IL-18 and endogenous IL-12; however, this activity is unrelated to the spleen cell lytic activity.

Animals↗
PubMed1975

Inhibition of proliferation of lymphoma cells and T lymphocytes by suppressor cells from spleens of tumor-bearing mice.

We have recently demonstrated suppressor cells in spleens of mice bearing tumors induced by Moloney murine sarcoma virus (MSV) which were non-T cells and inhibited phytohemagglutinin Molney (PHA)-induced DNA synthesis of syngeneic normal spleen cells. From the present study, the suppressor cells appeared to be macrophages since they were radioresistant, inactivated by carrageenan, and removed by adherence columns and an iron/magnet technique. We have also found that suppressor cells were still fully active when added 16 hr after the mitogen, thus indicating that early mitogen-induced changes were not the target of suppressive action. It appeared that suppressor cells inhibited metabolic events related to the initiation of DNA synthesis and that they had a selective effect on proliferation-dependent lymphocyte effector functions. PHA-induced cytotoxic reactivity which in our system is largely independent of DNA synthesis was not depressed but actually enhanced in MSV spleens. Cytotoxicity of MSV spleen cells against syngeneic lymphoma cells was unaffected by suppressor cells whereas lymphocytes stimulation by mitomycin C-treated syngeneic lymphoma cellls was inhibited. MSV spleen cells also inhibited DNA synthesis of cultured murine lymphoma cells. This function was only slightly diminished after treatment with anti-omicron serum plus guinea pig complement. Furthermore, spleen cells from MSV tumor-bearing nude mice were as effective as spleen cells from their heterozygous littermates, thus suggesting that T lymphocytes are not the main effector cells of inhibition of lymphoma cell DNA synthesis. The inhibitor cells were radioresistnant, inactivated by carrageenan, and removed by adherence columns and the iron/magnet technique. These data strongly suggest that the inihibitor cells of lymphoma cell DNA synthesis are macrophages and that they belong to the same group of cells as the suppressor cells of PHA-induced lymphocyte proliferation.

Animals↗
PubMed1999

Experimental study on the segmental perfusion and preservation of spleen.

OBJECTIVE: Spleen transplanlation has developed to be an effective strategy for hemophilia A. But it has not been reported up to date that which kind of established solutions is most suitable for perfusion and preservation of spleen. This study aimed to establish some experiences with the comparison among Hartmann's solution, Collins' solution and WMO-I solution, in order to instruct the clinical spleen transplantation. METHODS: After the splenic artery and vein were dissociated clearly, three kinds of perfusion solutions began to perfuse the corresponding segments of spleen with a randomized sequence. When the efferent fluids from the splenic vein became clear, the perfused spleen segments were preserved for different durations with the same perfusing solution to calculate the survival rate of splencocyte (SRS) and were examined with light and electron microscopy. RESULTS: Among the three solutions, SRS with WMO-I solution was significantly higher than those of the other two (P<0.001). The perfused spleen with WMO-I solution showed the slightest morphological changes and a significant longer preservation duration than those with the other two (P<0.05 or P<0.01). CONCLUSION: Among the three solutions, WMO-I solution was most suitable for perfusion and preservation of spleen.

Animals↗
PubMed2001

[Effects of recombinant human macrophage colony stimulating factor (rhM-CSF) on stromal cell derived during the time of mice colony formation unit-spleen (CFU-S) and its role on CD34+ cells expansion in vitro].

OBJECTIVE: To investigate the effects of stromal cell derived from mice spleen during in vitro expansion of CD34+ hematopoietic stem cells from umbilical cord blood. METHODS: Irradiated and non-irradiated mice at day 10, 12 and 14 were sacrificed and their spleens were taken for collecting spleen cells. The cells were stimulated with recombinant human macrophage colony stimulating factor(rhM-CSF) for collecting adherent spleen derived stroma cells. The effects of spleen derived stromal cells which treated with mitomycin served as a feeder layer, combined with different cytokines on in vitro expansion of purified cord blood CD34+ were assayed. Clonogenic assay and flow cytometry were employed to analyze phenotype of expanded cells and their ability to form different colony in vitro. RESULTS: 1) rhM-CSF efficiently stimulated spleen derived stromal cells to proliferate; 2) The mice stromal cells obtained during the time of colony formation-unit spleen (CFU-S) promoted the CD34+ cells to form colony in semisolid medium and, combined with cytokines, thereby efficiently expanded the hematopoietic cells from cord blood. After two weeks incubation, CD34 positive cells were 100 times more than original cells cultured and expanded cells still have the ability to form multi-lineage colony in vitro. CONCLUSION: rhM-CSF can stimulate the stromal cells derived from CFU-S to proliferate and support the survival and expansion of CD34+ cells separated from cord blood.

Animals↗
PubMed1992

Increased synthesis of extracellular spleen glycosaminoglycans in an experimental myeloproliferative syndrome.

The changes occurring in the hematopoietic extracellular matrix in an experimental myeloproliferative syndrome were explored by comparing the glycosaminoglycan (GAG) composition of normal mouse spleens and spleens infected with myeloproliferative sarcoma virus (MPSV). Large quantities of hyaluronate and of sulfated GAGs accumulated in the extracellular matrix of infected spleens, as shown by histoimmunoassay and alcian blue staining, respectively. The splenic GAGs were either labeled with 35S-sulfate injected in vivo or unlabeled. The spleens were fractionated to separate hematopoietic cells from the stromal component containing extracellular matrix material and fibroblasts, and the GAGs were extracted from each fraction. Specific degradative treatments and electrophoresis indicated that sulfated GAGs were mostly chondroitin sulfate and heparan sulfate. Three hours after in vivo injection of 35S-sulfate, the amount of 35S-GAGs was increased approximately fivefold per mg stromal proteins. The bulk of these 35S-GAGs (70%) was recovered in the stromal fraction. The higher amount of sulfated GAGs in leukemic spleen was due both to the presence of more producer cells (infected fibroblasts and hematopoietic cells) and to a stimulation of GAG synthesis per cell, as evidenced 35S-labeling in in vitro experiments. Chondroitin sulfate was the main sulfated GAG present in the culture medium of both hematopoietic and fibroblastic cells and in the pericellular material released by trypsin from fibroblastic cells. High amounts of chondroitin sulfate, which has a possible role in the detachment of hematopoietic cells from the stromal cells, may favour the release of hematopoietic cells from the spleen into the peripheral blood. Heparan sulfate was produced by fibroblastic cells and it was principally present in their pericellular material. Considering the capacity of heparan sulfate to retain cytokines, as demonstrated by others in vitro, large amounts of heparan sulfate may result in the retention of large amounts of the cytokines, which production is enhanced in the infected spleen. This phenomenon may contribute to promote the hematopoietic stem cell proliferation characteristic of the MPSV-induced myeloproliferative disease.

Animals↗
PubMed1977

Effects of lymphocytes from Marek's disease-infected chickens on mitogen responses of syngeneic normal chicken spleen cells.

PHA responses have been measured in lymphoid cell cultures prepared by mixing normal chicken spleen cells with spleen or thymus cells from syngeneic chickens infected with the oncogenic herpesvirus MDV. Results of these studies may be summarized as follows: 1) spleen cells from MDV-infected chickens with visceral lymphomas inhibit the PHA response of normal spleen cells possibly by release of soluble inhibitory factors in response to the mitogen; 2) lymphoid cells from asymptomatic MDV-infected chickens, although hyporeactive themselves to PHA, can have a stimulatory effect on PHA responses of normal spleen cells in mixed cultures; 3) spleen cells from MDV-infected chickens, effectively protected from viral oncogenesis by HVT vaccination, show normal reactivity to PHA in spearate cultures and may react in mixed cultures like normal lymphocytes, with neither a pronounced stimulatory nor inhibitory effect on the PHA response of normal spleen cells.

Animals↗
PubMed1992

Cell cycle status of murine megakaryocyte and granulocyte-macrophage colony-forming cells in bone marrow and spleen.

The cell cycle status of megakaryocyte colony-forming cells (Meg-CFC) and granulocyte-macrophage colony-forming cells (GM-CFC) from the spleen and bone marrow of C57BL mice was evaluated by determining the effects of hydroxyurea (OHU) or cytosine arabinoside (Ara-C), both in vivo and in vitro, upon colony-forming cells (CFC). The concentrations of cells in culture (2 x 10(6) to 4 x 10(6)/ml for spleen and 0.25 x 10(5) to 1.0 x 10(5)/ml for bone marrow) did not alter cell cycle status of either Meg-CFC or GM-CFC. Determination of cell cycle status following in vivo administration of OHU indicated that 25.2% of Meg-CFC and 28.1% of GM-CFC in the spleen, and 26.0% of Meg-CFC and 29.5% of GM-CFC in the bone marrow, were in cycle. In vitro incubation of CFC with OHU showed that in the spleen 25.1% of Meg-CFC and 24.2% of GM-CFC were engaged in DNA synthesis, whereas in bone marrow 28.5% of Meg-CFC and 29.2% of GM-CFC were synthesizing DNA. Incubation with Ara-C, in vitro, gave similar results, with 26.0% of Meg-CFC and 26.2% of GM-CFC in the spleen, and 27.1% of Meg-CFC and 31.4% of GM-CFC in the bone marrow, in cycle. In summary, significant differences were not observed between the cell cycle status of Meg-CFC and GM-CFC, whether derived from spleen or bone marrow. In vitro and in vivo measurements (with OHU) and in vitro measurements with two cytotoxic drugs (OHU versus Ara-C) also provided similar results. The data suggest that the regulation of DNA synthesis in both Meg-CFC and GM-CFC in the murine spleen and bone marrow is similar.

Animals↗
PubMed2005

[Protective effect of orgnoselenium from Se-enriched lactobacillus on lipid peroxidation reaction and NK cell activity in spleen of liver injury mice].

Changes of lipid peroxidation reaction and NK cell activity in spleen of CCl4-induced liver injury mice with adding orgnoselenium from Se-enriched lactobacillus were studied to discuss the protective effect of orgnoselenium and its mechanism. Sixty healthy mice (female: male=1:1) were chosen and divided randomly into four groups: control group (group C), orgnoselenium group (group Se), CCl4-injection group (group CCl4) and CCl4-injection plus orgnoselenium group (group CCl4-Se). The liver injury was induced by abdominal injection of CCl4 (0.07ml/100g body weight) on every other day over four weeks. The spleens were collected at the 2nd and 4th week, and spleen NK cell activity, spleen homogenate GSH-Px, SOD, CAT activities and MDA concentration were determined. The results showed that during the entire experimental period, spleen homogenate GSH-Px, SOD and CAT activities in groups C, Se and CCl4-Se were higher or significantly higher than that in group CCl4, and three antioxidant enzyme activities in groups Se and CCl4-Se had no apparent differences from that in group C except that there were significant increases of SOD activity at the 4th week. Spleen homogenate MDA content of group CCl4 increased markedly compared with that of groups C, Se and CCl4-Se, MDA level of group CCl4-Se was close to that of group C, and that of group Se was lower. During the entire experimental period, NK cell activity of group Se was the highest and significantly higher than that of group C at the 4th week, a lowest value was observed in group CCl4, which was lower or markedly lower than that of groups C, Se and CCl4-Se, there were no significant differences between group CCl4-Se and group C. It is suggested that orgnoselenium from Se-enriched lactobacillus can enhance antioxidation ability in normal mice and play an effective role by means of improving and enhancing the spleen antioxidation enzymes and NK cell activities in the process of intervening liver injury.

Animals↗
PubMed2006

Simultaneous increases in immune-competent cells and nitric oxide in the spleen during Plasmodium berghei infection in mice.

BACKGROUND AND PURPOSE: Nitric oxide and other reactive nitrogen intermediates (RNI) are thought to be important mediators of both immunological and pathological responses of the vertebrate host to malaria infection. The role of RNI has been studied most often by assay of stable RNI metabolites (nitrites, nitrates) in blood. This study evaluated the nature of the RNI response of mice to malaria by analyzing the subsets of immune-competent cells within the organ displaying increased RNI in vivo. METHODS: We measured RNI production indirectly, as stable metabolites of nitric oxide activity in tissue homogenates (brain, liver, spleen) from mice infected with Plasmodium berghei. Only spleen exhibited an RNI concentration response during rising parasitemia. Subsets of immune-competent cells (B cells, CD19+), macrophages/monocytes (MOMA2+) and T cells (CD4+, CD8+) in the spleen were assayed by fluorescence activated cell scan flow cytometry. RESULTS: The spleen was confirmed as a major source of RNI during mid-phase P. berghei infection. Significant increases in CD19+ and MOMA2+ spleen cells were evident during the mid-phase of P. berghei infection in MF1 mice when RNI are maximally elevated. CONCLUSIONS: The time courses of the cellular and RNI responses indicate that CD19+ and MOMA2+ cells may be responsible for the increase in RNI in the spleen. However, experiments in vitro are needed to make a definitive identification of the cell type(s) responsible for the increase in RNI in the mouse spleen during P. berghei infection.

Animals↗
PubMed2006

[Clinicopathologic characteristics of metastatic carcinomas to spleen].

OBJECTIVE: To study the clinicopathologic characteristics of metastatic carcinomas to the spleen. METHODS: Sixteen cases of metastatic carcinoma to the spleen were retrieved from archival clinical, surgical pathology and autopsy records. The demographic data (including sex and age of patients), clinical symptoms, primary sites, tumor histologic types, gross appearance of spleen and growth patterns within the spleen were analyzed. RESULTS: Among the 16 patients studied, 12 were males and 4 were females. The male predilection was obvious. The age ranged from 48 to 90 years, the median age 66.5 years. Major clinical symptoms included discomfort in the left upper quadrant, pain, emaciation and loss of appetite. Splenomegaly was noted in some patients and computerized tomography could show space-occupying lesions in the spleen. In general, lung was the most common primary site for splenic metastasis and accounted for 43.8% of all cases (7/16). In male patients, primary lung tumor was found in 50.0% cases (6/12). On the other hand, primary ovarian tumor was commonly seen in females (2/4). Histologically, undifferentiated carcinoma of lung was frequently encountered (25.0%, 4/16), including 3 cases of small cell undifferentiated carcinoma and 1 case of large cell undifferentiated carcinoma. Other histologic tumor types included bronchioloalveolar carcinoma (2 cases), colonic adenocarcinoma (2 cases), ovarian serous papillary adenocarcinoma (2 cases), and prostatic adenocarcinoma (2 cases). The commonest histologic tumor type found in male patients was pulmonary undifferentiated carcinoma. The growth patterns of metastatic carcinoma in spleen included nodular, diffuse and multinodular. Most cases presented as a single splenic nodule. Sometimes, tumors with high metastatic potential (5/16) showed diffuse and multinodular growth patterns. Examples of these tumors included small cell undifferentiated carcinoma (3 cases), pulmonary adenocarcinoma (1 case) and prostatic adenocarcinoma (1 case). CONCLUSIONS: Metastatic carcinoma to the spleen is rare. Understanding of the clinicopathologic characteristics is helpful in guiding clinical management and pathologic diagnosis.

Adenocarcinoma↗
PubMed2006

[Immunomodulation after combined spleen and kidney transplantation in swine].

AIM: Organ transplantation is the most effective treatment for several degenerative end-stage diseases. While the mainstream immunosuppression can achieve satisfactory results, the therapy has either side effects and flaws. The golden target to reach should be a stable tolerance with the transplanted organ accepted without a long term drug administration. Recent studies demonstrated a tolerogenic effect of spleen cells. Aim of this study is to evaluate a model of combined spleen and whole organ transplantation in a significant preclinical setting in swine. METHODS: Twenty-five outbred Landrace/Large-White swine underwent combined spleen/kidney transplantation (SKTx). The experiments were stratified into 3 groups per randomization. Group 1 (N=7) received kidney transplantation (KTx) alone with no immunosuppressive treatment. Group 2 (N=9) had a combined KTx and whole graft spleen Tx. Group 3 (N=9) had KTx and spleen cells (DST), injected through the portal vein. Renal lab tests were collected to evaluate the onset of rejection. Survivals were evaluated as well. The end-point of the study was at onset of kidney failure or at the limit of 60 postoperative day (POD) in non-rejecting animals. Tissue samples were collected to evaluate grade and severity of rejection. RESULTS: Controls died from kidney failure within 10(th) POD. Group 2 and 3, had a delayed renal graft rejection and an overall prolonged graft survival. Whole graft and spleen cells injection share this effect, while spleen administration through the portal route proved a superior effect, which is significant compared to controls (Kaplan Meier survival analysis P<0.05). CONCLUSIONS: These results, from a non immunosuppressed setting, suggest that spleen plays a key role as an immunomodulatory organ.

Animals↗
PubMed2006

Evaluation of the splenic vein diameter and longitudinal size of the spleen in patients with Gamna-Gandy bodies.

PURPOSE: The aim of this retrospective study was to compare the splenic vein diameter and longitudinal size of the spleen in patients with portal hypertension in whom Gamna-Gandy bodies were present in their spleen with those of cirrhotic patients without Gamna-Gandy bodies and a control group. MATERIALS AND METHODS: Between July 2001 and February 2006, patients in whom Gamna-Gandy bodies were detected in their spleen and the number of patients who had been undergone magnetic resonance (MR) imaging with the diagnosis of chronic liver disease were determined. A total of 43 cases with Gamna-Gandy bodies were noted. Out of these patients, a case of lymphoma was excluded from the study. Additional 3 cases with splenic vein thrombosis were not included in statistical analysis. Accordingly, the splenic vein diameter and longitudinal size of the spleen in 39 patients (group 1: 12 women, 27 men; mean age, 38.5 years) with portal hypertension in whom Gamna-Gandy bodies were detected in their spleen on T1-weighted gradient-echo MR images between July 2001 and February 2006 were measured. The values obtained were compared with those of 29 cirrhotic patients without Gamna-Gandy bodies (group 2: 14 women, 15 men, mean age 48.2 years) and control group (group 3: 13 women, 18 men, mean age 46.8 years). The differences between the groups were analyzed with ANOVA and student-t test. RESULTS: Gamna-Gandy bodies were detected in 6.3% (42/670) of patients with chronic liver disease. The mean longitudinal axis of the spleen (20.2+/-4.2 cm) in group 1 was significantly greater (p<0.001) than in group 2 (14.4+/-3.9 cm). The mean splenic vein diameter was significantly larger in group 1 (14.3+/-4.0 mm) than those in groups 2 and 3 (11.2+/-3.2 mm and 7.8+/-1.4 mm, respectively). CONCLUSION: The splenic vein diameter and longitudinal size of the spleen in portal hypertensive patients with Gamna- Gandy bodies are significantly larger than that of cirrhotic patients without Gamna-Gandy bodies and that of control group.

Adolescent↗
PubMedDate not supplied

[Dynamics of apoptosis and proliferation in the rat thymus and spleen during perinatal development].

The levels of spontaneous apoptosis and proliferation of the rat thymic and spleen cells, as well as their regulation by the hypothalamo-hypophysial system were studied during perinatal development. The apoptotic and proliferating cells in the thymus and spleen were assayed using flow cytometry with the DNA-specific dye propidium iodide. The level of apoptosis in the thymus reached 25% on day 18 of embryogenesis (E 18) and decreased to 5% thereafter. In the spleen, the level of apoptosis gradually increased from 15 to 37% during the period of E18 to day 30 of postnatal development (P30). The level of dividing cells in the thymus was 20-25% at all developmental stages studied. In the spleen, it was at a maximum on E18 (32%) and decreased almost twice on E21 (17%). On P7, the amount of proliferating cells again increased to 22% and then gradually decreased to 7% by P30. The surgical ablation of hypothalamus in utero on E18 did not affect cell apoptosis or proliferation in the thymus and spleen. The surgical ablation of both hypothalamus and pituitary led a twofold decrease of the level of apoptosis in the spleen and insignificant increase of the level of proliferation in the thymus. Thus, the numbers of cells in the embryonic thymus is regulated not only by the thymus itself, but also by the hypothalamo-hypophysial system. The programmed cell death in the embryonic spleen appears to be regulated by the hypothalamo-hypophysial system as well.

Animals↗
PubMed1991

[Radiation effect on anti-tumor activity of C3H mouse spleen cells to MH134 hepatoma cells].

Tumor-specific immunity was induced in C3H mice by immunizing with syngeneic MH134 hepatoma cells. The radiation sensitivity of tumor-specific effector cells in the immunized spleen cells and that of non-specific effector cells in normal spleen cells were compared. The spleen cells, both immunized and normal, were irradiated in vitro, then mixed with the tumor cells. The anti-tumor activity of the cells was measured by Winn assay and by a cytostatic test in vivo with diffusion chambers, on the basis of growth inhibition of tumor cells. The growth of tumor cells was inhibited by immune spleen cells more effectively than by normal spleen cells. The anti-tumor activity of immunized and normal spleen cells decreased dose-dependently in the respective ranges of 2.5-20 Gy and 2.5-10 Gy irradiation. In the normal spleen cells, anti-tumor activity was mainly detected in the fraction of non-adherent cells, not in adherent cells. The anti-tumor activity of non-adherent cells was diminished with 2.5 Gy irradiation. These results indicated that the radio-resistance of anti-tumor effector cells in C3H mice was increased by immunization with syngeneic MH134 hepatoma cells. Based on these and other findings in this experimental system, we concluded that tumor-specific effector cells that were radiosensitive at 10-20 Gy might involve delayed-type hypersensitivity (DTH) effector cells (macrophages) and that non-specific effector cells that were radiosensitive at 2.5-10 Gy might involve natural killer cells and lymphokine-activated killer cells.

Animals↗
PubMed1977

Reversal of SV40 tumor-mediated suppression of spleen cell cytotoxicity by antibody.

Spleen cells obtained from hamsters bearing PARA-7 tumors greater than 1.0 cm were not reactive in microcytotoxicity assays unless preincubated overnight. The events occurring during in vitro incubation which lead to reversal of tumor-mediated suppression of cellular immunity were investigated. After 24 hr of incubation, supernatants overlying spleen cells from tumor-bearing hosts contained a factor which blocked cytotoxicity of simian virus 40 (SV40)3-sensitized spleen cells at the PARA-7 target cell level but not at the effector cell level. The preparations did not mediate antibody-dependent cellular cytotoxicity (ADCC). Opposite results were obtained in assays of culture medium overlying spleen cells from hosts with a tumor burden less than 0.1 cm. Although ADCC activity was present, no significant blocking was detectable. Treatment of inactive spleen cells with anti-hamster gamma-globlin in the presence of complement (anti-HGG + C) prevented activation and formation of blocking factor but did not impair the cytotoxic activity of already activated cells. Addition of SV40 antiserum to anti-HGG + C-treated cells led to effector cell activation, whereas heterologous virus-immune sera did not. Control studies established that the antibody-mediated recovery of cytotoxicity was not due to arming. Further studies showed that PARA-7 tumor antigen extract blocked at the effector cell level, not at the target cell level. Addition of PARA-7 extract to spleen cell supernatants mediating ADCC resulted in formation of a factor which blocked at the target cell level but not at the effector cell level. These data are compatible with the following interpretation. Spleen cell unresponsiveness is due to antigen blockade. Recovery of cytotoxicity occurs because antibody synthesized during the incubation period promotes elution of antigen from the effector cell surface. Thus, activation is accompanied by the generation of tumor antigen-antibody complexes.

Animals↗