Biomaterial Database

A soluble factor produced by lamina propria mononuclear cells is required for TNF-alpha enhancement of IFN-gamma production by T cells. 1999

J L Prehn, and C J Landers, and S R Targan

Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, CA 90048, USA.

The role of TNF-alpha in the mucosal inflammation of Crohn's disease has been demonstrated by the prolonged clinical responses and/or remissions among patients receiving i.v. infusion of anti-TNF-alpha. A correlation between TNF-alpha and elevated IFN-gamma production is suggested by the reduction in the number of IFN-gamma producing lamina propria mononuclear cells (LPMC) found in colonic biopsies from anti-TNF-alpha-treated patients. The aim of this study was to define the mechanism of TNF-alpha-augmented mucosal T cell IFN-gamma production. In this paper we present evidence that cultured LPMC secrete a factor which acts on preactivated T cells in concert with TNF-alpha to augment IFN-gamma production. This activity is independent of IL-12 and IL-18, the well-documented potentiators of IFN-gamma expression, and is not produced by PBMC. Peripheral blood PHA-activated T cells incubated in supernatants from LPMC became responsive to TNF-alpha by increasing IFN-gamma output upon stimulation. These results are consistent with a model in which LPMC, but not PBMC, release an unidentified substance when cultured in vitro with low dose IL-2. This substance can act on preactivated peripheral T cells, as well as on lamina propria T cells, conditioning them to respond to TNF-alpha by increased IFN-gamma secretion upon stimulation. Expression of this factor in the gut mucosa could contribute to up-regulation of the Th1 response in the presence of TNF-alpha, and could be important for mucosal immunoregulation.

UI	MeSH Term	Description	Entries
D007369	Interferon Inducers	Agents that promote the production and release of interferons. They include mitogens, lipopolysaccharides, and the synthetic polymers Poly A-U and Poly I-C. Viruses, bacteria, and protozoa have been also known to induce interferons.	Inducers, Interferon
D007371	Interferon-gamma	The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.	Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D007413	Intestinal Mucosa	Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.	Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D007963	Leukocytes, Mononuclear	Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.	Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D008213	Lymphocyte Activation	Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.	Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D010835	Phytohemagglutinins	Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture.	Kidney Bean Lectin,Kidney Bean Lectins,Lectins, Kidney Bean,Phaseolus vulgaris Lectin,Phaseolus vulgaris Lectins,Phytohemagglutinin,Hemagglutinins, Plant,Lectin, Kidney Bean,Lectin, Phaseolus vulgaris,Lectins, Phaseolus vulgaris,Plant Hemagglutinins
D002474	Cell-Free System	A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)	Cellfree System,Cell Free System,Cell-Free Systems,Cellfree Systems,System, Cell-Free,System, Cellfree,Systems, Cell-Free,Systems, Cellfree
D006358	Hot Temperature	Presence of warmth or heat or a temperature notably higher than an accustomed norm.	Heat,Hot Temperatures,Temperature, Hot,Temperatures, Hot
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000276	Adjuvants, Immunologic	Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.	Immunoactivators,Immunoadjuvant,Immunoadjuvants,Immunologic Adjuvant,Immunopotentiator,Immunopotentiators,Immunostimulant,Immunostimulants,Adjuvant, Immunologic,Adjuvants, Immunological,Immunologic Adjuvants,Immunological Adjuvant,Adjuvant, Immunological,Immunological Adjuvants

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