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1.
The development of the in vitro cytostatic capacity of splenic lymphocyte subpopulations from C3H mice carrying the syngeneic Gardner tumor was examined at different times after intramuscular tumor injection. Most mice died between 3 to 6 weeks after tumor injection, while some rejected their tumors or survived longer than 3 months. Cell separation procedures and monoclonal antibodies against T-cell subsets were used to identify the cells responsible in anti-tumor immunity. Cytostatic capacity against tumor cells developed in the T-cell enriched subpopulation of splenocytes 3 days after tumor injection and was partly abrogated by anti-Lyt-1. Effector function of Lyt-2+ T cells and B cells developed later and peaked at around 10 days after tumor injection. Another cell population with cytostatic capacity which was not blocked by anti-Lyt-1, anti-Lyt-2, or anti-Ly-5 was noted to develop early after tumor injection and lacked both T-cell and B-cell markers ("null"). This subpopulation was eluted with T cells from nylon wool columns and comprised up to 50% of the T-enriched fraction of splenocytes in later stages of tumor growth. An interesting characteristic of these "null" cells was susceptibility to T-cell suppression both in early and later stages of tumor growth except in regressor mice which lacked suppressor T cells. The cytostatic capacity of the "null" cells could be restored either by removal of Thy-1+ cells from the T-enriched fraction by panning, or the addition of anti-Thy-1 or F(ab')2 fragments of anti-Thy-1 to the lymphocyte-tumor reaction mixtures. Most mice examined after 10 days of tumor growth were immunosuppressed to varying degrees. Unseparated splenocytes from these mice were not cytostatic but removal of T cells allowed the B cells to exert their cytostatic capacity. A strong underlying B-cell cytostasis was shown to be present in long survivor mice even though their unseparated spleen cells were only weakly cytostatic. T cells did not play a role in the regression of tumors or long-term survival of tumor bearer mice. Splenocytes from regressor mice were strongly cytostatic, their anti-tumor activity residing in the "null" and B-cell populations.  相似文献   

2.
Cyclic nucleotide-independent protein kinases that preferentially phosphorylated casein and phosvitin as substrate were detected in the nuclei of human and porcine thyroid tissues, and compared with those from rat liver. Enzymes were extracted from the isolated nuclei with a buffer solution containing 0.4 M NaCl, and analyzed by DEAE-Sephadex and phosphocellulose column chromatographies. The chromatographies, together with the characterization of the enzymes, demonstrated that human and porcine thyroid tissues contained two major casein kinases in the cell nuclei, the properties of which revealed that they are to be identified as protein kinases NI and NII.  相似文献   

3.
Many studies have already been reported with regard to the serological cross-reactivities between the polymorphic determinants of murine Ia antigens and human HLA-DR antigens. In this paper, we examined the biological cross-reactivity of the polymorphism of Class II antigens in the xenogeneic antigen-presenting cell (APC)-T-cell interaction. The data indicate that purified protein derivative (PPD)-specific human T cells were not stimulated by PPD-pulsed murine APC from B10.S(9R) which possess I-As and I-Ek molecules serologically cross-reacting with human Class II antigens. On the contrary, B10.S(9R) T cells primed to PPD were stimulated by PPD-pulsed human APC. The failure of the murine APC-human T-cell interaction was not caused by the suppressive effect in culture with ongoing xenogeneic mixed lymphocyte reactions (MLR) or other cell culture conditions. Thus, a hierarchy of antigen-presenting ability in the xenogeneic APC-T-cell interaction was shown to exist.  相似文献   

4.
Cells from the spleen, lymph nodes, and peritoneum of DBA/2 mice bearing a subcutaneous tumor mediate nonspecific suppression of an in vitro antibody response to sheep red blood cells (SRBC) when cocultured with a normal T-cell subset(s). The spleen cells from the tumor-bearing mouse required for the suppression bear the Lyt 1 and Ala 1 surface markers characteristic of "inducer" T cells and activated cells, respectively. The activity of this cell population is also sensitive to irradiation. The normal T-cell subset which cooperates in the suppression bears the Qa-1 surface antigen which has been associated with suppressor cell precursors in several systems but lacks detectable surface Lyt 1 and 2 markers. Suppression of antibody responses in spleen cell cultures from tumor-bearing mice alone could also be elicited, but only when increased numbers of cells were cultured. These data are consistent with the theory that a tumor-activated, Lyt 1+ T-cell subset has the capacity to nonspecifically suppress immune responses by activating a Qa-1+ subset(s) of T suppressor cells, perhaps via feedback signals.  相似文献   

5.
Splenic leucocyte effector cells from 3-month-old C3H/HeJ mice which were antibody negative for influenza A virus were found to be spontaneously cytotoxic for mouse L929 fibroblasts infected with influenza virus, but not for uninfected cells. The cytotoxic activity was significantly enhanced if the effector cells were preincubated with splenic leucocytes from older 6- or 9-month-old antibody-negative mice before being added to the target cells. Enhancement appeared to be due to a cooperative effect between leucocytes from mice of different ages. Preincubation of effector cells with autologous sera markedly suppressed spontaneous cytotoxicity, but the suppression was significantly less with sera from 7- or 10-month-old mice than with sera from 3-month-old mice. Most cytotoxic activity was observed with a nylon wool-adherent subpopulation of leucocytes, although some cytotoxicity remained in the non-adherent fraction. The results suggested that spontaneous cytotoxicity was due to two subpopulations of cells, possibly adherent monocyte-macrophages and nonadherent natural killer cells.  相似文献   

6.
The embryonic rat pancreas, removed on the 14th day of gestation and cultivated in vitro, accumulates differentiated levels of exocrine enzymes and insulin. In the period corresponding to days 16–22 in vivo, 99% of the final insulin content accumulates. During this period we have studied the development of competence for insulin secretion, the regulation of this secretion by glucose and other secretatogues, and the rate of synthesis following a secretory challenge. Our results demonstrate that the capacity for insulin secretion develops in parallel with the accumulation of insulin in secretory granules since β granules appear at day 16. On day 16, after 48 hr of culture, both glucose and caffeine are required for detectable insulin secretion. At later stages, insulin release can be effectuated by glucose alone. In the fetal pancreas at day 20 of development, glucose is ten times more efficient than caffeine and fourfold more efficient than caffeine combined with either glucagon, cholera toxin or dibutyryl cyclic AMP. Glucagon, cholera toxin or cyclic AMP in the presence of caffeine increases equally (about tenfold) both the “basal” and the glucose-induced level of secretion. This suggests that glucose and caffeine act independently but synergistically. The integrity of the cells is maintained under the stimulation conditions, and there is a selective increase in insulin synthesis measured during 18 hr following stimulation of insulin release.  相似文献   

7.
8.
Changes in the T-lymphocyte alloreceptor repertoire associated with aging by exploring the frequency of cytotoxic T-lymphocyte precursors (CTLp) available for activation by various major histocompatibility complex (MHC) haplotypes in mice of different ages have been investigated. There was no consistent pattern of change in CTLp frequencies. Thus, for instance, while the frequency of responder C57Bl/6 CTLp for ATH alloantigen decreased with age, the frequency for C3H alloantigen increased. There was no significant change in the overall frequency of splenic CTLp (assessed irrespective of antigen specificity). No evidence was found that CTL produced by activated CTLp of aged mice were less specific in their lytic capacity that CTL produced by CTLp of young mice. However, by assaying responder CTLp cultures at limiting dilution we obtained evidence that the “burst size” (mean lytic capacity per responder well assayed at limiting dilution) was diminished with age of the donor of the CTLp pool. Furthermore, we obtained evidence that the apparent affinity of CTL for their target antigen was consistently decreased when those effector cells were derived from a pool of CTLp of aged mice. All of these changes reflected in mature T cells derived from aged mice were already apparent in the bone marrow stem cell pool of aged individuals and were not due to environmental influences alone, as assessed by the phenotype of T cells derived from young or old bone marrow stem cells transplanted to young or aged recipient mice. A final study has examined evidence for more subtle changes in the T-cell alloreceptor repertoire, reflecting heterogeneity in young or aged mice in the recognition repertoire associated with a given antigenic specificity. By preparing F1 anti (parent anti-F1)-suppressor cells directed against CTL from young parental mice (a, b, c), or aged parental mice (x, y, z), we have explored the heterogeneity in the anti-C3H alloreceptor repertoire in individual young or aged C57Bl/6 mice. Suppression by immunized F1 animals was assessed in tissue culture (inhibition of mixed lymphocyte culture (MLC) responses) or in vivo (inhibition of lethal GvHD induced by inoculation of parental lymphocytes into sublethally irradiated F1 hybrid mice). Irrespective of the assay system used, the data suggests that the receptor repertoire of aged T lymphocytes uses recognition structures different from those of young individuals, and that there is less individual-to-individual variation in the receptor repertoire of aged mice than in young mice.  相似文献   

9.
We have carried out a comparative study of the developmental profiles of the enzyme acetylcholinesterase, and of its collagen-tailed and globular structural forms, solubilized in the presence of 1 M NaCl, 1% (w/v) sodium cholate and 2 mM EDTA, in the chick retina and optic lobes. The overall acetylcholinesterase activities, both per mg protein and per embryo or chick, are substantially higher in tectum than in retina, from embryonic day 16. The A12 collagen-tailed form of the enzyme is present in similar amounts in the embryonic retina and optic tectum; however, while the A12 activity increases significantly in retina after birth, both by percentage and in absolute terms, the tectal tailed enzyme follows a declining developmental profile, reaching a minimum after 6 months of life. On the other hand, the globular G4 species shows developmental profiles, both in retina and tectum, rather similar to those obtained for the overall enzyme activity, while the G2 and G1 forms are present in comparable concentrations in both tissues. Besides, G4 is the predominant globular form in the chick optic lobe after hatching, G2 and G1 being enriched in the embryonic tectum. In the case of retina, however, all the globular forms contribute more evenly to the total acetylcholinesterase activity, along the developmental period considered.The potential significance of some of the postnatal developmental profiles is discussed in terms of the progressive adjustment of retina and tectum to the requirements of visual function.  相似文献   

10.
Distinct classes of human T-cell activation antigens   总被引:2,自引:0,他引:2  
The characterization of three groups of antigens expressed by activated human T lymphocytes and detected by monoclonal antibodies is reported. Antigens defined by OKT19, OKT21, and OKT22 do not appear on in vitro activated T cells until increases in DNA synthesis become apparent and are not detected on most Interleukin 2 (IL-2)-independent cell lines and normal peripheral blood lymphocytes, monocytes, and granulocytes. Cell surface molecules reactive with the monoclonal antibodies OKT23 and OKT24 are displayed prior to any notable increase in DNA synthesis and are present on IL-2 independent cell lines, irrespective of lineage. T23 and T24 do not appear on peripheral blood cells and their distribution more closely resembles that of the T9 antigen (the receptor for transferrin) than antigens of the other groups. The third group of antigens, T14 and T20, have been classified as "early" antigens relative to DNA synthesis. They are expressed by distinct populations of normal lymphoid cells as well as by some IL-2-independent cell lines. Display of each group of activation antigens on T lymphocytes can be induced by either phytohemagglutinin, purified protein derivative from tuberculin, or allogeneic non-T cells, is not restricted to the OKT4+ or OKT8+ subsets, and is predominant on cells exhibiting the light-scattering properties of blast cells. The relative lack of expression of these antigens among normal peripheral blood cells make them attractive candidates for identifying changes in the status of immune activation.  相似文献   

11.
When meiotic maturation of primary oocytes of the starfish Asterias forbesi is induced by 1-methyladenine, rapid and striking changes in the pattern of protein synthesis detectable by electrophoresis occur after germinal vesicle breakdown. These include a decline in relative labeling with [35S]methionine of several polypeptides synthesized in the oocyte, and increased labeling and new appearance of several polypeptides. Fertilization does not result in other detectable changes. The population of total mRNA translatable in a rabbit reticulocyte lysate cell-free system does not change, but the distribution of mRNAs between polysomes and the postribosomal supernatant reflects the changes observed in vivo. Thus these changes are regulated at the translational level. A review of the literature indicates that translationally mediated changes in patterns of protein synthesis during maturation of oocytes may be a widespread phenomenon.  相似文献   

12.
Alterations in the high and low affinity insulin receptor concentrations in developing rat liver were investigated. The number of high affinity receptors in partially purified plasma membranes from fetal rats increased from Days 19 through 22 of gestation, with no further increase in binding during the postnatal period. Fetuses of diabetic rats had approximately three times as many high affinity insulin receptors as age-matched fetuses of normal rats; however, by 1 day after birth the receptor number decreased to the normal level. Neither the number of low affinity receptors nor the affinity of insulin binding to high or low affinity receptors changed during development or between offspring of normal and diabetic rats. These changes in the number of high affinity hepatic insulin receptors from prenatal animals did not correlate with the concentration of plasma insulin. When suckling pups were rendered diabetic the changes in the number of high affinity insulin receptors correlated with alterations in plasma insulin concentrations. The number of high affinity sites/microgram DNA in hepatocytes from Day 18 fetal rats was not altered when cells were cultured for 48 h in medium containing 0, 250, or 5000 μU/ml of added insulin. When cultured hepatocytes derived from 1-day-old and adult rats were maintained in medium with added insulin concentrations of 250 or 5000 μU/ml the number of high affinity receptors/microgram DNA decreased as compared to the number of high affinity receptors in hepatocytes cultured in medium with no added insulin. This decrease in receptor number was accompanied by an increase in the affinity of insulin binding to its high affinity receptors. The data show that (i) only the high affinity insulin receptor number increases in rat liver during the prenatal period, (ii) fetuses of diabetic rats show a greater increase in high affinity receptors than do fetuses of normal animals, and (iii) the phenomenon of down regulation for high affinity insulin receptors is not observed in fetal rat liver, but is acquired in the immediate postnatal period.  相似文献   

13.
By use of pulse-chase exposure of dissociated cells of rat fetal spinal cord or brain to [3H]thymidine (TdR) and unlabeled TdR it has been shown that oligodendroglial precursors which do not express galactocerebroside (GalC) divide first and later differentiate to express GalC. The rate of proliferation of more mature GalC+ oligodendrocytes is considerably lower than that of their GalC- precursors. It has been found that oligodendrocyte precursor cells are extremely sensitive to [3H]TdR irradiation. Exposure to as little as 0.03 microCi/ml for 24 hr proved to be harmful, particularly during a critical period before birth. This critical period corresponded to the peak of division of oligodendrocyte precursor cells.  相似文献   

14.
Studies were performed to characterize the human peripheral blood non-T cells forming colonies in semisolid cultures stimulated with Staph protein A (SpA). Negative selection experiments revealed that colony precursors largely consisted of cells bearing Fc receptors, complement receptors (CR), surface immunoglobulin (sIg), and Ia-like antigens. Most colony precursors expressed sIgM and sIgD, but not sIgG. Also, colony-forming cells were shown to be distinct from non-T cells proliferating in SpA-stimulated liquid cultures as evidenced by the greater sensitivity of colony precursors to anti-K,λ, or -Ia plus complement depletion. Two distinct categories of colony-forming cells could be distinguished by the expression of CR. CR-positive cells were responsible for greater than 85% of the colonies formed in the absence of optimal T cell numbers. Although under identical conditions CR? cells demonstrated minimal colony growth, the addition of optimal T cell numbers significantly augmented colony responses. Thus, colony precursors express surface markers characteristic of B cells relatively advanced in the developmental pathway. However, less advanced cells are capable of colony growth in the presence of optimal T cell numbers.  相似文献   

15.
A large series of mouse monoclonal antibodies was found to inhibit the proliferation of T-cell growth factor (TCGF)-dependent human T-cell blasts as measured by the incorporation of tritiated thymidine. The specificity of the antibody appeared to be irrelevant for inhibition and two T-cell-specific antibodies did not prevent the absorption of TCGF by treated T cells. It is suggested that the antibodies function by the indirect release of suppressor factors by Fc receptor-bearing TCGF-dependent cells.  相似文献   

16.
The results of previous studies on the temporal sequence of limb vascularization suggest that the prospective myogenic and chondrogenic areas of the mesoderm are distinguished by a differential vascularization pattern prior to the overt expression of muscle- and cartilage-specific phenotypes. The experiments presented here are designed to reveal the dynamic aspects of vascular flow in the limb by the observation of how an inert, particular tracer (india ink) is mobilized and dispersed at specific points in the mesoderm. Data are presented as a temporal sequence of fluid flow "maps" which detail both the rate and the direction of vascular flow in the limb. It is proposed that not only does the vasculature compartmentalize the mesoderm into prospective myogenic and chondrogenic zones but also that these broad areas are subcompartmentalized into discrete microenvironments that are spatially distinct with regard to their capacity for transporting the carbon particles. The developmental significance of this observation may be that limb mesodermal cells are granted precise, "positional" information in the form of the specific nutrient and oxygen levels they encounter during critical, or decisional, phases of morphogenesis.  相似文献   

17.
The growth of the P815 mastocytoma in syngeneic DBA/2 mice led to an activation of Ly1+2- T cells. These T cells produced a soluble factor or factors in culture which, when added to normal spleen cells or B cells in the presence of syngeneic Ly1 cells, caused a genetically unrestricted augmentation of the plaque-forming response toward sheep red blood cells (SRBC). The culture supernatant of the activated T cells did not support the proliferation of an interleukin-2 (IL-2)-dependent cell, nor exhibit properties of late-acting TRF. Active supernatants appeared to affect directly B cells during the first 48 hr of culture with SRBC in such a way as to make them more responsive to antigen-specific Ly1-cell help.  相似文献   

18.
Lymph and supernatants derived from efferent lymphocytes leaving the popliteal lymph nodes of sheep responding to human red cells or dinitrophenylated bovine serum albumin were examined for the presence of T-cell growth factor (TCGF). Efferent cells from normal sheep, but not from antigen-stimulated sheep, were found to release low levels of TCGF when incubated in medium for 12 hr in the absence of any exogenous stimulus. High levels of TCGF were found in normal lymph and also in immune lymph collected from sheep during the first 6 hr of immune responses. There were no detectable levels of TCGF in lymph collected later in the response. The lymphokine appeared to be a single molecular species of 10,000–20,000 molecular weight as assessed by exclusion chromatography. Efferent cells expressing receptors for TCGF were found in efferent lymph during the first 12 hr of the response. The results demonstrate for the first time that TCGF is produced in vivo and that asynchrony exists between TCGF production and expression of receptors for TCGF on efferent cells released by the stimulated node. Based on the known kinetics of previously reported synergistic factors, mitogenic factors, and T-cell-replacing factors in sheep efferent lymph and their physical characteristics it was concluded that the TCGF detected in lymph is distinct from these factors.  相似文献   

19.
Intratumor host cells of methylcholanthrene-induced fibrosarcoma(s) were shown to enhance the in vivo outgrowth of syngeneic homologous tumors (MCIA, Mc2A, Mc2B) but not two heterologous T-lymphomas (EL4 and TLX9) in the Winn adoptive transfer assay. This enhancing activity was not restricted only to the latent period of tumor growth but was also observed during the period of active in vivo tumor proliferation. Tumor enhancement was mediated by a population of cells adherent to nylon wool and glass and insensitive to irradiation (with 850 rads) or to treatment with anti-Thy 1.2 serum and complement. Macrophages from peritoneal exudates of normal mice, used as control host cell population, showed similar tumor-enhancing activity. These findings suggest that tumor infiltrating host cells, predominantly macrophages appear to be the cell type responsible for tumor enhancement and active promotion of tumor growth (in vivo).  相似文献   

20.
Some cellular requirements have been examined for the stimulation of lymphocyte production in mouse bone marrow by injected sheep red blood cells (SRBC). The increased genesis of marrow lymphocytes after a single dose of SRBC assayed radioautographically after [3H]thymidine labeling was unimpaired in the marrow of mice treated with anti-IgM antibodies from birth to eliminate B lymphocytes, and in congenitally athymic mice lacking T lymphocytes. However, pretreatment of mice with silica to depress macrophage function completely abolished the SRBC effect both on the total lymphocyte production and on the number of B and null small lymphocytes in the marrow. Comparative studies were performed on the thymus and spleen. The results demonstrate that the stimulation of marrow lymphocyte production by SRBC is mediated by a silica-sensitive mechanism, does not require B or T lymphocytes, and is independent of the humoral immune response. Thus, extrinsic agents may amplify the production of primary B cells and other lymphocytes in the bone marrow by an antigen-nonspecific mechanism, putatively mediated by macrophages.  相似文献   

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