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PubMed2006

Corticotropin-releasing hormone modulates human trophoblast invasion through carcinoembryonic antigen-related cell adhesion molecule-1 regulation.

Abnormalities in the process of trophoblast invasion may result in abnormal placentation. Both the embryonic trophoblast and maternal decidua produce corticotropin-releasing hormone (CRH), which promotes implantation. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), which is expressed in extravillous trophoblasts (EVTs) of normal human placenta, may also function in tro-phoblast/endometrial interactions. We investigated whether locally produced CRH plays a role in trophoblast invasion, primarily by regulating CEACAM1 expression. We examined cultures of freshly isolated human EVTs, which express CEACAM1, and an EVT-based hybridoma cell line, which is devoid of endogenous CEACAM1. CRH inhibited EVT invasion in Matrigel invasion assays, and this effect was blocked by the CRH receptor type 1 (CRHR1)-specific antagonist antalarmin. Additionally, CRH decreased CEACAM1 expression in EVTs in a dose-dependent manner. After transfection of the hybridoma cell line with a CEACAM1 expression vector, the invasiveness of these cells was strongly enhanced. This effect was inhibited by addition of blocking monoclonal antibody against CEACAM1. Furthermore, blocking of endogenous CEACAM1 in EVTs inhibited the invasive potential of these cells. Taken together these findings suggest that CRH inhibits trophoblast invasion by decreasing the expression of CEACAM1 through CRHR1, an effect that might be involved in the pathophysiology of clinical conditions, such as preeclampsia and placenta accreta.

Antigens, CD↗
PubMed2001

Modulation of CD8+ T cell response to antigen by the levels of self MHC class I.

The response of H-Y-specific TCR-transgenic CD8(+) T cells to Ag is characterized by poor proliferation, cytolytic activity, and IFN-gamma secretion. IFN-gamma secretion, but not cytotoxic function, can be rescued by the B7.1 molecule, suggesting that costimulation can selectively enhance some, but not all, effector CD8(+) T cell responses. Although the H-Y epitope binds H-2D(b) relatively less well than some other epitopes, it can induce potent CTL responses in nontransgenic mice, suggesting that the observed poor responsiveness of transgenic CD8(+) T cells cannot be ascribed to the epitope itself. Previously reported reactivity of this TCR to H-2A(b) is also not the cause of the poor responsiveness of the H-Y-specific CD8(+) T cells, as H-Y-specific CD8(+) T cells obtained from genetic backgrounds lacking H-2A(b) also responded poorly. Rather, reducing the levels of H-2(b) class I molecules by breeding the mice to (C57BL/6 x B10.D2)F(1) or TAP1(+/-) backgrounds partially restored cytotoxic activity and enhanced proliferative responses. These findings demonstrate that the self MHC class I gene dosage may regulate the extent of CD8(+) T cell responsiveness to Ag.

Animals↗
PubMed1975

Modulation of the immune response by antigen-reactive lymphocytes after cultivation with gangliosides.

GM1 ganglioside isolated from mouse brain was found to be capable of inhibiting the thymocytotoxicity of AKR anti-Thy 1.2 antiserum and to a lesser extent anti-BAtheta antiserum. GD1b ganglioside of mouse brain and thymocytes inhibited the thymocytotoxicity of rabbit anti-BAtheta anti-serum for mouse thymocytes. When GM1 ganglioside, in the form of cholesterol-lecithin liposomes, was incubated with spleen cell cultures in the presence of SRBC, depressed anti-SRBC hemolytic plaque responses were observed. This effect could be neutralized by first absorbing the GM1 liposomes with anti-Thy-1.2 antibodies. The kinetics of GM1 numbers when the ganglioside was added even as late as the 4th day of culture. Results of experiments in which GM1 ganglioside was incubated with either bone marrow cells or with thymocytes suggest that the target cell for GM1 liposomes is the B lymphocytes.

Animals↗
PubMed1975

Modulation of the immune response to transplantation antigens. IV. Enhanced growth of tumour allografts in mice immunised with papain-solubilised transplantation antigen.

C57/Bl mice have been immunised with papain solubilised CBA transplantation antigen and subsequently challenged with a CBA tumour. Variations in antigen dose, immunisation schedules and routes of injection were compared. Two procedures in particular led to enhanced growth of the tumour allograft: (a) a single injection of antigen seven days before graft, and (b) a two-pulse immunisation spaced over 42 days. Mice given the seven-day course showed impaired cell-mediated cytotoxicity and blocking antibody at the time of challenge which was succeeded by blocking antigen in the circulation after challenge. Mice immunised by the two-pulse course developed heightened cell-mediated cytoxicity, but showed a persisting level of blocking antibody in the serum. Thus, although both immunisation regimes enhanced tumour growth, they did so by different mechanisms.

Animals↗
PubMed1975

Modulation of the immune response to transplantation antigens. V. A comparison of the effects of antilymphocytic serum and enhancing alloantiserum on effector mechanisms of allograft rejection.

Administration of antilymphocytic serum (ALS) or alloantiserum at the time of graft both stimulate enhanced growth of a tumour allograft, but the effect of alloantiserum is weaker and more dependent on dose. Both antisera suppress (or delay) the development of lymphocyte-mediated cytotoxicity, and partly inhibit the development of activated, cytostatic macrophages. Apart from these central or afferent effects, ALS added to an in vitro culture of immune effector cells and EL4 target cells strongly inhibits cytotoxicity, while in this model, alloantiserum is less effective in this respect. The relevance of the effects observed in vitro to in vivo facilitation of allografts is discussed.

Animals↗
PubMed1992

Modulation of the posthemorrhage bacterial polysaccharide antigen-specific antibody response by interleukins 2 and 4.

Abnormalities in immune response play a major role in the increased susceptibility to infection after hemorrhage and trauma. Several studies have shown decreased release in vitro of interleukin-2 (IL-2) following blood loss. To better define in vivo the interactions between T and B cells, as well as the effects of treatment with the T cell-derived cytokines IL-2 and IL-4, mice were injected with concanavalin A at predetermined times posthemorrhage, and the percentages and numbers of splenic plasma cells producing antibody to the bacterial polysaccharide antigen levan (from Aerobacter levanicum) were determined. Decreased numbers and percentages of levan specific splenic plasma cells were found in animals treated with concanavalin A both immediately and 2 to 4 days after hemorrhage. Treatment in vivo with recombinant IL-2, but not IL-4 or anti-IL-2 receptor antibodies, following blood loss was able to increase the numbers of levan specific plasma cells to levels as high or higher than those found in normal, unhemorrhaged animals, but was unable to affect the decreased percentage of levan specific splenic plasma cells. These results suggest that the use in vivo of IL-2 may restore bacterial antigen specific antibody responses to normal levels after blood loss.

Animals↗
PubMed1991

Modulation of the cluster 1 and mucin antigens in human small cell lung cancer and other epithelial tumour cell lines after treatment with the differentiation inducing agent, sodium butyrate.

The expression of the human small cell lung cancer (SCLC) cluster 1 antigen and the human milk fat globule membrane (HMFG) antigen were studied in three SCLC, three lung adenocarcinoma, six ovarian adenocarcinoma and three colorectal adenocarcinoma cell lines before and after culture in the presence of the differentiation inducing agent, sodium butyrate. Before treatment, only SCLC and well differentiated ovarian cell lines expressed the cluster 1 antigen. After 4 days culture with sodium butyrate, expression of cluster 1 antigen was induced in poorly differentiated ovarian, colorectal and lung adenocarcinoma cell lines whereas existing antigen expression was enhanced in SCLC and well differentiated ovarian cell lines. The expression of the HMFG antigen was also modified. Induction of cluster 1 antigen correlated with increased levels of alkaline phosphatase in the treated cell lines, this enzyme being associated with a more differentiated state in colon and ovarian carcinoma cell lines. The pattern of induction of cluster 1 antigen expression suggests that several different epitopes of this antigen are recognised by the ten SCLC cluster 1 antibodies studied.

Adenocarcinoma↗
PubMed1990

Bone marrow stromal cells modulate both kappa light chain and Ly1 antigen expression on Ly1+ pre-B cell lines in vitro.

Murine Ly1+ pre-B cell lines, including 70Z/3 and three pre-B cell lines derived from long-term bone marrow cultures, exhibited selective adherence to bone marrow stromal cells. In contrast, splenic B cells, the A20 B-cell lymphoma, and four Ly1- B cell lines derived from long-term bone marrow cultures failed to adhere substiantially to bone marrow cultures failed to adhere substiantially to bone marrow stroma. Ly1+ pre-B cell lines were induced to express kappa light chains by exposure to either lipopolysaccharide (LPS), recombinant interleukin-1 (IL-1), or stromal cells. However, induction of kappa light chains failed to prevent pre-B cell adherence to stromal cells. Supernatants derived from primary bone marrow stromal cells decreased Ly1 expression on the Ly1+ pre-B cell lines. These experiments suggest that (1) expression of immunoglobulin light chains by developing Ly1+ pre-B cells is mediated by bone marrow stromal cells; (2) loss of specific adherence to stroma is progressive and occurs post-light chain induction; and (3) soluble products of stromal cells may downregulate expression of surface Ly1 on otherwise Ly1+ pre-B cells. The importance of these observations to the development of both the Ly1- and Ly1+ B cell lineages in the mouse is discussed.

Animals↗
PubMedDate not supplied

Inhibition of growth of subcutaneous xenografts and metastasis of human breast carcinoma by swainsonine: modulation of tumor cell HLA class I antigens and host immune effector mechanisms.

Swainsonine, an indolizidine alkaloid, can decrease the organ colonization potential of metastatic murine tumor cells by augmentation of host immune effector mechanisms. In this report the above findings were extended by the demonstration that systemic administration of swainsonine strongly suppressed the growth of human breast carcinoma subcutaneous xenografts and experimentally induced lung metastases. This inhibition was not due to a direct effect of swainsonine on cell growth. However swainsonine treatment of tumor cells resulted in enhanced expression of HLA Class I antigens, and HLA class I mRNA. Swainsonine was a potent immunodulator as evidenced by the increased (a) cytotoxicity of splenocytes and macrophages, and, (b) proliferative potential of splenocytes and bone marrow cells. These data suggest that swainsonine-induced inhibition of tumor growth and metastases may be mediated via activation of host effector cells and/or alteration of tumor cell antigenicity.

Alkaloids↗
PubMed1988

Transforming growth factor-beta 1 modulates the expression of class II histocompatibility antigens on human cells.

We have examined the effects of transforming growth factor-beta (TGF-beta 1) on the expression of the class II histocompatibility Ag, HLA-DR: 1) induced by human rIFN-gamma (rHuIFN-gamma) in human melanoma, Hs294T cells and 2) constitutively expressed in a subclone Hs294T cell line. The expression of HLA-DR Ag on Hs294T cells was induced by rHuIFN-gamma in a dose- and time-dependent manner with maximal levels obtained with 10 ng/ml rHuIFN-gamma after 48 h exposure. Treatment of Hs294T cells with natural porcine platelet-derived or human rTGF-beta 1 (1 to 100 ng/ml) in the presence of rHuIFN-gamma (0.1 to 10 ng/ml) reduced the percentage of cells positive for this Ag by approximately 40 to 50%, as determined by flow cytometry. This suppressive effect of TGF-beta 1 was not restricted to Hs294T cells inasmuch as rHuIFN-gamma induced HLA-DR surface Ag expression on PBMC-derived adherent cells was also significantly inhibited by TGF-beta 1. Northern blot analysis of cytoplasmic RNA extracted from Hs294T cells indicated that the decreased levels of HLA-DR cell-surface Ag correlated with decreased levels of mRNA transcripts encoding this Ag. TGF-beta 1 also effectively reduced the levels of HLA-DR mRNA in 1) cells that had been pretreated with rHuIFN-gamma and were expressing maximal levels of HLA-DR surface antigen and 2) cells that constitutively expressed HLA-DR surface Ag without exogenous rHuIFN-gamma treatment.

Antigens, Surface↗
PubMed1988

Modulation of the expression of major histocompatibility antigens on splenic hairy cells--differential effect upon in vitro treatment with alpha-2b-interferon, gamma-interferon, and interleukin-2.

The mechanism of action responsible for the beneficial effect of alpha-interferon (alpha-IFN) in patients with hairy cell leukemia (HCL) is still unknown. Direct antineoplastic and immunomodulating effects on both the host immune system and the hairy cells themselves have been implicated. To evaluate whether lymphokines have any regulatory effect on antigens of the major histocompatibility complex (MHC) on hairy cells and whether this corresponds to prognostic clinical parameters, we studied splenic hairy cells from ten previously untreated patients. The samples were incubated with recombinant human alpha-IFN, gamma-IFN (gamma-IFN), and interleukin-2 (IL-2). In an indirect staining procedure, cells were labeled with monoclonal antibodies (MoAb) to HLA ABC and HLA DR surface structures and subjected to cytofluorimetric analysis. Results concerning the expression of MHC class I and HLA DR antigens were mixed for incubation of hairy cells with gamma-IFN and IL-2, whereas alpha-IFN had a distinct effect on HLA DR antigen expression. alpha-IFN strongly enhanced the intensity of staining with HLA DR MoAb in six patients, and it increased the percentage of MoAb-positive cells in five of these samples. In contrast, the staining intensity in samples from four patients was reduced considerably on alpha-IFN treatment. In this group, two samples showed a sharp alpha-IFN-induced decrease in the number of HLA DR MoAb-positive cells from originally high values, and in one sample the very low percentage of positive cells was unaffected by alpha-IFN exposure. These two groups of patients whose hairy cells displayed contrasting HLA DR expression on incubation with alpha-IFN in vitro, were found to differ in their subsequent clinical course.

Animals↗
PubMed1995

Dietary fiber in weaning foods of young children.

OBJECTIVE: An evaluation of the opportunity to introduce fiber in the diet of weaning infants. METHODS: A descriptive review of the literature to assess the role of fiber in the following dietary interventions: (1) definition of the nutrient amounts that meet the weaning infant's physiologic needs; (2) modulation of digestive and absorption processes; and (3) improving the nutritional balance between the 6th and the 12th months of life and setting habitual dietary patterns for subsequent years. FINDINGS: Whole cereals, nonstarchy vegetables, fruits, and legumes lower the caloric and proteic density of meals, modulate nutrient and antigen absorption, and provide bulk material. They supply proteins of low biological value, minimal amounts of lipids (mostly essential polyunsaturated), complex carbohydrates, and soluble fiber, which are fermented into short-chain fatty acids by the colonic flora, and insoluble fiber that modulates intestinal function. Minerals, trace elements, and vitamins add to the value of fiber-containing foods in the diet. Recent nutritional surveys indicate that the diets of 12-month-old infants tend to include too much animal proteins and to be too protein-dense, which could be corrected with an increase of fiber-containing foods. CONCLUSIONS: Fiber-containing foods share unique characteristics with nutritional and metabolic implications for the weaning infant. Whole cereals, green vegetables, and legumes should be routinely introduced during the weaning process to achieve a better nutritional balance and to accustom children to diets with fiber content. The daily intake of fiber should be gradually increased to 5 g/d during the second semester of life.

Diet↗
PubMed1994

Quantitation of immunogold with an interactive image analysis system. A new, practical approach to antibody-induced modulation, internalization and intracellular transport of surface antigens in viable hematopoietic cells.

This work aimed to evaluate the value of computerized quantitative analysis in ultrastructural studies on internalization and intracellular transport of leukocyte antigens traced with immunogold in viable lymphoid cells. The time of analysis and the results were compared with those obtained with a standard method based on counting gold particles on electron micrographs. A commercially available, personal computer-based, single-screen system was used for capturing and processing the ultrastructural images, counting gold particles and presenting data. The viable lymphoblasts of RAJI and NALM-6 cell lines were labeled with B4 (anti-CD19) murine monoclonal antibody followed by rabbit antimouse immunoglobulins coupled to 12.8-nm colloidal gold, cultured for six hours to allow internalization of CD19 antigen, collected after various periods of time and processed for electron microscopy. Each sample was analyzed by counting the gold particles on 30 randomly chosen, equatorial cell sections. Surface-bound particles and those located within certain intracellular compartments (that is, cytoplasmic vesicles, multivesicular bodies and lysosomes) were counted separately. No significant differences were found between the results obtained using electron micrographs and those yielded by on-screen analysis of digitized images. However, the time of analysis varied considerably--approximately eight and two hours, respectively. Also, using computerized analysis saved the cost of photographic processing. In conclusion, the system provided a reliable, rapid and inexpensive alternative for quantitation of immunogold-labeled leukocyte antigens at the ultrastructural level.

Antibodies↗
PubMed1991

Allotype-linked immune response genes: roles in network control of the immune system.

Studies on allotype-linked immune response genes and related genes are overviewed with particular attention to our current results in unique models. Significance of actions of various immune response genes in relation to allelic polymorphism of molecules in the immune system is discussed. The molecules involve immunoglobulins, T cell receptors, major histocompatibility complex and a number of cell interaction molecules, many of which belong to the immunoglobulin superfamily. Differential roles of V-linked and C-linked immune response genes for network control of the immune system, preparing the V structure repertoire, controlling antigen presentation and modulating the effector mechanism, are suggested.

Animals↗