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1.
A spontaneous large granular lymphocyte leukemia from a F344 rat was transplanted to 36 syngeneic recipients to study the interactions among leukemia, T lymphocytes, and the development of immunemediated hemolytic anemia. Six rats were euthanatized at biweekly intervals, and spleen weight, total spleen cellularity, and differential spleen cell counts were correlated with hemograms and osmotic fragility. Sequential changes in splenic architecture were correlated with hematologic parameters. Monoclonal antibodies defining all T lymphocytes (W3/13), T helper-inducer cells (W3/25), and T suppressor cells (OX-8) were used to identify T cells in immunocytochemical techniques on spleen sections, as well as in fluorescence activated cell sorter analysis of spleen cell suspensions. The onset of hemolytic anemic at 7 weeks after transplantation coincided with the first detection of tumor cells in the spleen and peripheral blood. Tumor cells first accumulated in the marginal zones, and then they infiltrated the red pulp sinusoids. Although the leukemia caused dispersion of the splenic lymphoid tissue, there was no significant lymphopenia, and the relative number of helper (W3/25+) and suppressor (OX-8+) lymphocytes did not change. Because the induction of anemia was a relatively early event in splenic involvement, we concluded that anemia was unrelated to disruption of lymphoid architecture; furthermore, it does not appear to be caused by changes in the numbers of regulatory T lymphocytes.  相似文献   

2.
Twenty-two congenitally athymic nude (rnu/rnu) rats were transplanted with large granular lymphocyte leukemia derived from F344 rats and then compared with ten similar rats inoculated with a suspension of normal F344 rat spleen cells. The normal spleen cells and tumor cells from a spontaneous, naturally occurring leukemia did not grow or cause clinical disease in any of the rats. All rats inoculated with a serially passaged leukemia cell inoculum had local growth at the inoculation site that spread widely and resulted in progressive tumor growth. Death occurred between 16 and 38 days after inoculation. The 22 rats that received passaged tumor cells developed leukemia and splenomegaly. Spleens were diffusely infiltrated by tumor cells and had severe depletion of lymphocytes in the white pulp. Leukemic rats were thrombocytopenic and had hemolytic anemia characterized by increased osmotic fragility, red cell width, and many nucleated erythrocytes. The disease syndrome appears similar to that of F344 rats transplanted with the same inoculum. Because the host rats lacked T cells, it is concluded that the hemolytic anemia and thrombocytopenia that develop in transplanted rats are independent of T cell function.  相似文献   

3.
Large granular lymphocyte (LGL) leukemia was induced in 40 F344 rats by inoculating them with neoplastic cells to evaluate the effect of acute leukemia on bone remodeling and calcium balance. The rats developed leukemia and splenomegaly by 9 days after inoculation. The rats had reduced body weight (day 12), food intake (days 4, 8, 12), urine production (day 12), and fecal output (day 12). Serum calcium and phosphorus and urinary excretion of calcium and phosphorus were decreased on days 8 and 12 in leukemic rats. Static bone histomorphometry of trabecular bone in lumbar vertebrae demonstrated reduced bone area, no change in the number of osteoclasts, and reduced osteoclast perimeter at day 12. Dynamic bone histomorphometry revealed reduced double labeled perimeter, mineralizing perimeter, trabecular mineral appositional rate, and bone formation rate in rats with LGL leukemia at days 9 and 12. There was no change in periosteal mineral appositional rate. Rats with leukemia and intramedullary neoplastic cells had a reduction in bone formation rate that resulted in a loss of trabecular bone.  相似文献   

4.
A transplantable mononuclear cell leukemia (MCL) was established from spontaneous MCL in an F344 rat. In this work, we paid special attention to a nodular tumor, named MCL-YSK, developed at the subcutaneous transplant site. MCL-YSK was serially passaged in subcutaneous tissue of syngeneic rats up to the 19th generation. Transplants from MCL-YSK grew into nodules 3 cm in diameter and 11.3 g in weight 9 weeks after subcutaneous implantation. Neoplastic cells forming the nodules had azurophilic cytoplasmic granules, which ultrastructurally appeared to be lysosomes. The cells reacted positively for acid phosphatase and nonspecific esterase, but not for alkaline phosphatase, alpha-1 antitrypsin and lysozyme, nor reacted with anti-rat monocyte/macrophage monoclonal antibody and anti-rat CD-8 monoclonal antibody. They possessed Fc-receptor. Leukemic cells first appeared in the peripheral blood 6 weeks after transplantation when subcutaneous nodules reached an average diameter of one cm. Subsequently, leukemic changes progressed in recipients as MCL-YSK grew larger. The recipients died during the period from 8 to 12 weeks after transplantation, showing anemia, depression, splenohepatomegaly and lymph node enlargement. Diffuse or focal proliferation of sprinkled tumor cells was present in many organs. Hematologic changes suggestive of hemolytic anemia, elevated plasma enzymes and decreased drug-metabolizing enzymes, indicative of hepatic malfunction, were seen in transplant recipients. MCL-YSK was easily transplanted into athymic nude mice. The transplanted mice showed leukemic changes similar to those observed in rats with transplanted MCL-YSK.  相似文献   

5.
The early stage of large granular lymphocyte leukemia in the F344 rat   总被引：1，自引：0，他引：1  
In the early stages of large granular lymphocyte leukemia of F344 rats, splenic congestion and lymphocytic depletion of the splenic white pulp are the most significant and consistent histologic findings. The diagnosis of early leukemia was confirmed by immunocytochemical demonstration that the cell surface of leukemic large granular lymphocytes reacted with OX-8 monoclonal antibodies and by transplantation of the disease at early stages to healthy weanling rats.  相似文献   

6.
The lymphocyte subpopulations of peripheral blood of normal lambs and lambs experimentally infected with bovine respiratory syncytial virus (RSV) were analysed by flow cytometry, using a panel of monoclonal antibodies against specific lymphocyte epitopes. Experimental infection with bovine RSV was characterized by a significant rise in SBU-T8+ (CD8+ or cytotoxic) T cells and a significant reduction in SBU-T4+ (CD4+ or helper) T cells and B (LCA p220+) lymphocytes (P less than 0.05). The helper/suppressor (CD4/CD8) ratio was reduced from 3.91 on the day of experimental infection to 1.13 on 10 days after experimental infection (P less than 0.001). The total number of SBU-T4+ (CD4+) and B cells returned to pre-inoculation values 14 days after experimental infection but the helper/suppressor ratio remained depressed up to 21 days post-inoculation.  相似文献   

7.
Although spontaneously occurring neoplasms have been reported repeatedly in F344, SD and Wistar rats, which are commonly used strains for routine toxicologic and carcinogenicity studies, there are only a few reports of malignant lymphoma or lymphatic leukemia except for large granular lymphocytic leukemia (LGL) in F344 rats. Malignant lymphoma (lymphosarcoma) is thought to be uncommon in F344 rats. The authors encountered malignant lymphomas of the non-LGL leukemia type with characteristic pathologic features in WBN/Kob rats. The mean age at onset of the disease in all 13 affected rats (8 males and 5 females) was about 60 weeks. Common and characteristic clinical signs were abnormal gait with hind limb paralysis. Macroscopically, the enlargement of the lymph nodes, spleen and liver was slight to moderate. Scattered multiple white-to-gray nodules encompassed the aorta and assumed a bead-like appearance near the thoracic and lumbar vertebrae. Histopathologically, neoplastic proliferative changes were predominant in the bone marrow tissue of the entire body, and many tumor cells infiltrated the spleen and several lymph nodes. The most striking histological features were constant and severe infiltration of tumor cells in the adipose tissue and skeletal muscle adjacent the thoracic and lumber vertebrae. Immunohistochemically, all tumor cells were positive for B-cell markers (PAX-5, CD79a and CD45) and negative for CD3. From the results of immunohistochemistry and morphological examination, these tumors were diagnosed as malignant B-cell lymphomas.  相似文献   

8.
The effects of ovariectomy, ovariohysterectomy and hysterectomy on morphologically demonstrable characteristics of lymphoid organs, peripheral white blood cell counts and antibody production against sheep red blood cells (SRBC) were studied in female Lewis rats. Removal of ovaries induced enlarged thymus weight and cellularity. No differences were observed between the groups in spleen weight, while hysterectomy together with ovariectomy influenced relative uterus draining lymph node (UDLN) weight. The percent numbers of pan T, helper T lymphocytes, cytotoxic/suppressor T cells and IgG bearing cells (B lymphocytes) of all investigated organs showed only moderate changes caused by the surgical procedures. In contrast, removal of ovaries generated elevated total leukocyte and lymphocyte counts in peripheral blood. The changes in absolute blood lymphocyte counts were accompanied by similar variations in absolute T and B lymphocyte numbers. Ovariohysterectomy had slightly greater effects on these parameters than ovariectomy alone. In addition, ovaries and uterus had only moderate influences on systemic immune responses toward SRBC. In conclusion, the present results indicate that the removal of ovaries and uterus can modify morphological characteristics of lymphoid organs and peripheral blood but antibody production showed only moderate changes caused by the surgical procedures.  相似文献   

9.
An experimental study was carried out in order to evaluate the regeneration capacity of the neonatal intestinal wall in ischaemia and its repercussion over organs of the immune system such as the spleen. We isolated a reservoir of small intestine in adult Sprague-Dawley rats that, after having been everted and placed at a subcutaneous level, was grafted with a free small intestine segment of neonatal Sprague-Dawley rats and analysed 3, 15 and 30 days after grafting. Samples obtained were stained with Martin's trichromic stain and studied at the light microscopic level. A total regeneration of the crypt architecture, formed by absorptive enterocytes, was observed in the interior of the reservoirs. A quantitative immunohistochemical study with monoclonal antibodies against CD4, CD8, MHC I and MHC II was carried out in the spleen of these animals. An additional immunohistochemical study was also performed in the small intestine reservoirs and spleen of transplanted animals using nitric oxide synthase (NOS) antibodies. Three days after transplantation NOS immunoreactive cells were observed in the reservoirs with transplanted neonatal small intestine. Antigenic stimulation produced, in the spleen red pulp of transplanted animals, a significant increase (P < 0.001) in the percentage of NOS, CD8 and MHC I immunoreactive cells in relation with values observed in control animals. These morphometric changes could be related with the stimulation that nitric oxide produces in the proliferation of the cytotoxic T cells.  相似文献   

10.
1日龄雏鸡感染鸡传染性贫血病毒（CIAV）后,胸腺和脾脏T淋巴细胞增殖反应分别于14d和7～21d明显减弱（P相似文献   

11.
The lymphocyte subpopulations in the peripheral blood of normal sheep and sheep experimentally infected with Cytoecetes phagocytophila, the causative agent of tick-borne fever, were analysed by flow cytometry, using a panel of monoclonal antibodies against specific lymphocyte epitopes. Experimental infection with tick-borne fever was characterised by a significant reduction in the total number of circulating lymphocytes six days after experimental infection (P less than 0.001). This lymphocytopenia was associated with a significant reduction in the number of B (LCAp220+) and T (CD5+) lymphocytes (P less than 0.001) but there was a significant increase in the number of cells which were neither T nor B (CD5-LCAp220-) cells (P less than 0.01). The reduction in the number of T lymphocytes was due to reduced numbers of circulating CD4+ (helper) T cells, CD8+ (cytotoxic/suppressor) T cells and those with the pan T cell marker (CD5+) but without CD4 or CD8 epitopes (CD4-CD8-). All lymphocytes returned to preinoculation levels 13 to 16 days after experimental infection.  相似文献   

12.
Rhesus macaque (Macaca mulatta) peripheral blood T-lymphocyte subpopulations were assessed for the distribution of helper and suppressor/cytotoxic cells using the T-cell subset specific monoclonal antibodies T4 and T8 respectively. Highly purified T-lymphocytes (> 90% E-rosetted) were separated into subpopulations by rosetting with IgG (Tγ) and Igm (Tμ) sensitized bovine red blood cells, or by adsorption with insolubilized histamine. In this study, rhesus peripheral blood T-lymphocytes were found to express cell-surface determinates recognized by T4 and T8 monoclonal antibodies. Subset frequencies were found to be comparable to that found in humans (50% T4 and 33% T8). The helper subpopulation, Tμ, contained 30% T4 and 2% T8 type cells. These results suggest Tγ helper activity may be due to a selective depletion of suppressor cells, rather than an enrichment of helper T-cells. The suppressor subpopulations, Tγ, contained 9% T4 and 2% T8 type cells. These results suggest Tγ cells may represent either an undifferentiated suppressor cell or, perhaps, a separate suppressor subpopulation which does not express T8 differentiation antigens. The Tγ-subpopulation (depleted of cells with Fc-IgG receptors) was rich in helper T-cells (52% T4) and depleted of suppressor T-cells (6% T8). T-cells depleted of cells expressing IgM or IgG receptors, T-null, contained 47% T4 and 12% T8 type cells. Further, T-cells adsorbed with insolubilized histamine were selectively depleted (70% reduction) of T8 type cells, while the frequency of T4 type cells remained unaffected by histamine absorption. The majority of suppressor/cytotoxic T-cells (T8), therefore, appear to express cell-surface receptors for histamine.  相似文献   

13.
A panel of monoclonal antibodies (mAbs) with specificity for chicken lymphocyte surface antigens was established and characterized based on their reactivities against chicken lymphoid cells and tumor cell lines on flow cytometry. Three mAbs (7-3G-2, 7-2E-8, and JB-2) reacted preferentially with thymocytes, however, none of them reacted with Marek's disease derived T lymphoblastoid cell lines. Four mAbs (6-27A-1, 4-5C-5, Lc-4, and Lc-6) reacted with spleen cells and peripheral blood leukocytes as well as thymocytes. All seven mAbs reacted with chicken embryonic thymocytes from day 12 of embryonic life onward. All mAbs showed no reactivity against bursal lymphocytes.  相似文献   

14.
Clinicopathologic and immunophenotypic characteristics of large granular lymphocyte (LGL) neoplasia in 21 cats were examined. All cats were domestic short (19) or long hair (2) with a mean age of 9.3 years at diagnosis. Increased peripheral blood LGL counts were present in 18/21 cats. Neutrophilia (12/21 cats) and increased serum liver enzymes (7/12), total and direct bilirubin (7/13), BUN (5/14), and creatinine (2/14) were observed. Cats usually presented with advanced disease and none survived longer than 84 days (mean 18.8 days) postdiagnosis. Cytologically, LGLs had a mature (6/21), immature (13/21), or mixed (2/21) morphology. Necropsy lesions consisted of neoplastic lymphoid infiltrates in the jejunum, ileum, and duodenum in decreasing order of frequency. In the small intestine, mucosal ulceration (9/13) and epitheliotropism of neoplastic cells (9/13) were common. Neoplastic infiltrates were also present in the mesenteric lymph nodes (13/13), liver (12/13), spleen (8/13), kidneys (5/7), and bone marrow (5/7). A T cell phenotype (CD3epsilon+) characterized LGL neoplasia in 19/21 cases. A CD8alphaalpha+ cytotoxic/suppressor phenotype was present in 12/19 T cell tumors, 2 had a CD4+CD8alphaalpha phenotype, 3 had a CD4-CD8- phenotype, and 2 were CD4+ helper T cells. CD8beta chain expression was not detected in any instance. In two cats, a B or T cell origin could not be established. CD103 was expressed by 11 of 19 (58%) of the lymphomas tested. The immunophenotypic features shared by neoplastic LGLs in the cat and feline intestinal intraepithelial lymphocytes (IELs) support a small intestinal IEL origin for feline LGL lymphoma.  相似文献   

15.
1. The effects of antigen (Ag) injection on the distribution of lymphocyte populations of Cornell K‐strain male chickens were studied.

2. Two experiments were conducted. In the first, chickens were injected with Brucella abortus (BA), a purported T‐independent antigen. In the second, chickens were injected with sheep red blood cells (SRBC), a T‐dependent antigen. Peripheral blood lymphocytes (PBL) and spleen lymphocytes isolated at 0, 3, 6, 9, 12 and 24 h following Ag injection were stained with monoclonal antibodies (mAb) detecting B‐lymphocytes, CD4+ and CD8+ cells.

3. B‐lymphocytes in the blood or spleen showed no significant changes following either BA or SRBC injection. In contrast, CD4+ cells were decreased in the blood and increased in the spleen following BA and SRBC injections. CD8+ cells were decreased in both blood and spleen following BA injection but were unchanged in either blood or the spleen following SR8C injection.

4. These results indicate that there is a change in both spleen and circulating lymphocyte populations, especially T‐helper cells, following Ag injection. T‐helper cells are apparently the primary population involved in the initiation of humoral immunity.  相似文献   


16.
Effect of Fasciola gigantica infection on adrenal and thyroid glands was investigated using eight male, yearling Murrah buffaloes. The animals were randomly assigned to two groups of four buffaloes each (Group-A, infected; Group-B, non-infected control). Animals of Group-A were orally infected with 1000 F. gigantica viable metacercariae, keeping other four animals of Group-B as uninfected control. In the infected buffaloes, the clinical signs began appearing from 7th week postinfection (p.i.) and eggs were detected in the faeces between day 93 and 99 (95.5+/-1.25) postinfection (p.i.). The serum cortisol level, revealed a significant (P<0.05) rise during initial stage of the infection, followed by a continuous fall from 12th week onward. Peak cortisol level on 10th week (13.30+/-2.57ngml(-1)) was associated with eosinophilia (11.0+/-0.95%). However, non-infected controls maintained almost uniform cortisol levels (3.97+/-0.15-5.88+/-0.09ngml(-1)) throughout the period of the study. The pathological changes of adrenal glands were correlated with physiological dysfunction of the glands. The levels of T(3) and T(4) were significantly (P<0.05-0.01) low from 14th week onward and were synchronous with in situ migration, growth and development of F. gigantica. Significant reduction in the thyroid hormones was further supported by histopathological evidence of lymphocytic thyroiditis confirming hypothyroidism. A decrease in Hb, PCV, total erythrocyte counts and appearance of reticulocytes in the blood of the infected buffaloes suggested regenerative anemia, which could partly be due to hypothyroidism.  相似文献   

17.
To study the canine immune system we generated a mouse model engrafted with canine lymphocytes using NOD SCID IL2R common gamma chain ?/? (NSG) mice as recipients (Ca-PBL-SCID). Engraftment of canine peripheral blood lymphocytes (PBLs) was determined post-injection with 107 peripheral blood mononuclear cells (PBMCs) into irradiated NSG mice using flow cytometry and fluorescently labeled antibodies specific to canine helper T cells (CD45+ CD4+), cytotoxic lymphocytes (CD45+ CD8+), regulatory T cells (CD45+ CD4+ Foxp3+), and B cells (CD45+ Ig+ CD21lo). Canine CD45+ lymphocytes were detectable as early as day 1 in the peritoneal cavity, and beginning at 9 days in the blood, bone marrow, and spleen. CD4+ T cells, of which Foxp-3+ CD25hi cells constituted a minor percentage, were the predominant lymphocyte population at 9 days post engraftment contrasting with increasing proportions of CD8+ CTL's and Ig+ B cells beginning at 16 days. Canine immunoglobulin was initially detected in the serum of Ca-PBL-SCID mice at 9 days post-engraftment and peaked in concentration at day 36. From day 28 to 52 post-engraftment 30% of the Ca-PBL-SCID mice became markedly anemic and thrombocytopenic, yet gross and histopathologic examination of bone marrow, kidneys, spleen, liver, and intestine revealed no obvious lesions. Blood smear evaluation revealed agglutination of mature red blood cells, reticulocytes and a regenerative anemia. These findings demonstrate that NSG mice are capable of engraftment of canine PBLs yet develop graft versus host disease similar to Hu-PBL-SCID mice.  相似文献   

18.
Following an antigenic dose of 10 microgram or a tolerogenic dose of 200 microgram of Escherichia coli O138 lipopolysaccharide (LPS), BALB/c mice were examined on day 14 for percentages of theta-bearing cells. A considerable increase in T cells was noticed in lymphocytes from tolerant draining lymph nodes, and furthermore these cells did not possess receptors for LPS when tested for rosette inhibition. However, when the supernatant from 1 X 10(7) macrophages, pretreated with 150 microgram LPS, was given to tolerant mice on day 7, by day 14 tolerance was found to be broken, anti-LPS IgG was present in circulation and the draining lymph node contained T cells specifically committed to LPS. The change from suppressor to helper T cell activity is discussed in relation to enhancement of the immune response.  相似文献   

19.
The effects of cimetidine, an H2 receptor antagonist, on subpopulation of splenic lymphocytes were studied in mice. Cimetidine (50 mg/kg) was given to groups of mice by intraperitoneal injection. The splenic mononuclear cells from treated and control animals were evaluated for relative number of lymphocyte subpopulations (i.e. LYT1, LYT2, L3T4 and GAM cells) by flow cytometry. The percentages of LYT2 cells (suppressor equivalent) were significantly lower (5.5 vs 12.0%) in mice who were treated with cimetidine vs control animals. The percentages of L3T4 (helper equivalent) were not statistically different in any of the experimental groups.  相似文献   

20.
Pathology of the mononuclear cell leukemia of Fischer rats. II. Hematology   总被引：1，自引：0，他引：1  
Complete hemograms were evaluated for 57 rats with mononuclear cell leukemia and compared to hemograms obtained from 52 age- and sex-matched nonleukemic rats. All leukemic rats had marked hemolytic anemia and associated spherocytosis, reticulocytosis, anisocytosis, and polychromasia. The anemia varied with the stage of illness and was more severe in rts with advanced leukemia. Death appeared to be related to anemia. There was a marked neutrophilia with left shift, mild lymphopenia, and moderate to severe thrombocytopenia. Atypical mononuclear cells were detected in circulation in all but three rats. Total white blood cell counts ranged from 5.0-370 x 10(3) cells/ml. There was an increase in erythrocyte osmotic fragility with separation into two distinct populations of erythrocytes. Eight of nine rats were Coombs' positive indicating an immune-mediated pathogenesis for the anemia. Hemostasis tests revealed a markedly prolonged prothrombin time, hypofibrinogenemia, slightly increased to normal partial thromboplastin time, and undetected fibrin degradation products. These findings suggest significant liver disease associated with the leukemia.  相似文献   

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