UMLS:C0033036 - FACTA Search

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Query: UMLS:C0033036 (APC)
10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have concentrated here on the lymphokines which might serve to regulate the different pathways of precursor development. We suggest that, as a result of antigenic stimulation, specific precursor cells both proliferate and become committed to develop into either an effector cell, a memory cell or an anergized cell. Anergy has not been dealt with in this review, but it is likely to be one of the options available. The development of an effector population takes 4-7 d (quite analogous to the time it takes for CTLp to become CTL and for resting B to become Ab-forming cells). The effector populations are large, generally IL-2R-positive cells. These cells have upregulated many adhesion molecule systems [e.g., Pgp-1, LFA-1 and ICAM-1 (Swain unpublished)], but downregulated the Mel-14 homing receptor. Effectors are ready to respond to APC such as specific B cells with a rapid synthesis and secretion of lymphokines. The effector population is then quickly downregulated, both by the turn off of lymphokine synthesis/secretion and possibly by its own suicide. This kind of pattern makes teleological sense since the cells making such high titers of lymphokines could have many potent pleitropic effects. It also seems to be the strategy employed in the generation of other terminally differentiated effectors (such as CTL and plasma cells). The requirement for restimulation and the requirement for direct and perhaps prolonged contact between the helper effector and the APC-B cell can be expected to help ensure that these lymphokines are localized (reviewed in Swain & Dutton 1987, Swain & Croft 1990) and effectively delivered to specific responding cells. We postulate that at the same time, or perhaps subsequent to this, another set of signals drives precursors to generate prememory cells. Our studies suggest these emerging memory cells may be phenotypically unique and we postulate that they are specialized to become a "long-lived" population of memory cells that will persist indefinitely as a protective population of increased frequency for the antigen encountered and which is also able to respond more rapidly and effectively. The greater effectiveness of the memory response would thus be due to dramatically increased frequency, to characteristic and stable changes in adhesion molecule expression and to the fact that, in addition to IL-2, resting memory cells also secrete at least low titers of IL-3, IL-4, IFN-gamma and other lymphokines upon initial restimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Helper T-cell subsets: phenotype, function and the role of lymphokines in regulating their development. 168 76

Murine T lymphocytes recognize nominal Ag presented by class I or class II MHC molecules. Most CD8+ T cells recognize Ag presented in the context of class I molecules, whereas most CD4+ cells recognize Ag associated with class II molecules. However, it has been shown that a proportion of T cells recognizing class I alloantigens express CD4 surface molecules. Furthermore, CD4+ T cells are sufficient for the rejection of H-2Kbm10 and H-2Kbm11 class I disparate skin grafts. It has been suggested that the CD4 component of an anti-class I response can be ascribed to T cells recognizing class I determinants in the context of class II MHC products. To examine the specificity and effector functions of class I-specific HTL, CD4+ T cells were stimulated with APC that differed from them at a class I locus. Specifically, a MLC was prepared involving an allogeneic difference only at the Ld region. CD4+ clones were derived by limiting dilution of bulk MLC cells. Two clones have been studied in detail. The CD4+ clone 46.2 produced IL-2, IL-3, and IFN-gamma when stimulated with anti-CD3 mAb, whereas the CD4+ clone 93.1 secreted IL-4 in addition to IL-2, IL-3, and IFN-gamma. Cloned 46.2 cells recognized H-2Ld directly, whereas recognition of Ld by 93.1 apparently was restricted by class II MHC molecules. Furthermore, cytolysis by both clones 46.2 and 93.1 was inhibited by the anti-CD4 mAb GK1.5. These results demonstrate that CD4+ T cells can respond to a class I difference and that a proportion of CD4+ T cells can recognize class I MHC determinants directly as well as in the context of class II MHC molecules.
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PMID:Some cloned murine CD4+ T cells recognize H-2Ld class I MHC determinants directly. Other cloned CD4+ T cells recognize H-2Ld class I MHC determinants in the context of class II MHC molecules. 171 78

We have investigated the interaction between murine T lymphocytes and allogeneic APC in an in vitro proliferative mixed leukocyte reaction. Our results demonstrate that freshly isolated potentially alloreactive murine splenic T lymphocytes, in primary culture, can be induced to develop a state of allospecific proliferative hyporesponsiveness in vitro by exposure to 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide-modified allogeneic APC, a method similar to that previously used to induce nonresponsiveness in murine Ag-specific self-MHC-restricted T lymphocyte clones. This hyporesponsiveness was: specific for the allohaplotype of inducing APC, maintained for 96 h in vitro, not due to cellular inhibitory mechanisms, and associated with reduced ability to secrete IL-2 but not IL-3. Induction of this hyporesponsiveness was not due to altered expression of class II MHC gene products on the APC but was associated with markedly reduced T lymphocyte-APC adhesive interactions despite the lack of a detectable immunophenotypic change in lymphocyte function-associated Ag 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) expression on the modified APC. Therefore, we propose that TCR occupancy in the absence of normal T lymphocyte-APC adhesive clustering may induce T lymphocyte tolerance.
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PMID:Chemically modified antigen-presenting cells induce T lymphocyte allospecific hyporesponsiveness. 183 77

Delayed type hypersensitivity reaction (DTH) consists of a sequential cascade of steps depending on different types of T cells, as well as mast cells, endothelial cells and macrophages. Recently it has been shown that CD4+ TH1 lymphocytes ("inflammatory type") play a central role in DTH reaction. Activated TH1 cells produce a characteristic pattern of cytokines: IL-2, IL-3, TNF-beta, IFN-gamma. Using the contact sensitivity (CS) reaction on mice as a model system, the role of cytokines in the regulation of DTH is presented, particularly the significance of IL-3 and IL-6. The recent data can be interpreted to show that IL-6 released by activated macrophages (APC cells) in the induction phase of the CS reaction probably stimulate CD8+ T suppressor cells. These in turn inhibit the production of IL-2 and IL-3 by CD4+ TH1 cells followed by a state of unresponsiveness.
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PMID:Cell-mediated immunity: role of IL-3 and IL-6 in the regulation of contact sensitivity reaction. 209 80

A cytokine synthesis inhibitory factor (CSIF) is secreted by Th2 clones in response to Con A or antigen stimulation, but is absent in supernatants from Con A-induced Th1 clones. CSIF can inhibit the production of IL-2, IL-3, lymphotoxin (LT)/TNF, IFN-gamma, and granulocyte-macrophage CSF (GM-CSF) by Th1 cells responding to antigen and APC, but Th2 cytokine synthesis is not significantly affected. Transforming growth factor beta (TGF-beta) also inhibits IFN-gamma production, although less effectively than CSIF, whereas IL-2 and IL-4 partially antagonize the activity of CSIF. CSIF inhibition of cytokine synthesis is not complete, since early cytokine synthesis (before 8 h) is not significantly affected, whereas later synthesis is strongly inhibited. In the presence of CSIF, IFN-gamma mRNA levels are reduced slightly at 8, and strongly at 12 h after stimulation. Inhibition of cytokine expression by CSIF is not due to a general reduction in Th1 cell viability, since actin mRNA levels were not reduced, and proliferation of antigen-stimulated cells in response to IL-2, was unaffected. Biochemical characterization, mAbs, and recombinant or purified cytokines showed that CSIF is distinct from IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IFN-gamma, GM-CSF, TGF-beta, TNF, LT, and P40. The potential role of CSIF in crossregulation of Th1 and Th2 responses is discussed.
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PMID:Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. 253 Nov 94

Lymph node cells from 4-wk-old MRL/Mp-lpr/lpr mice, but not from MRL/Mp-+/+ mice, when cultured in vitro for 5 to 7 days, will spontaneously proliferate and produce IL-2. We examined the expression of several cell surface Ag on lymph node cells from MRL/Mp-lpr/lpr mice before and after in vitro culture. There is an increase in the expression of Thy-1, L3T4, IL-2R, T cell activating protein, T cell receptor, and T3 complex on the surface of cultured cells. Cultured cells produced IL-3, IFN-gamma, and small but detectable amounts of IL-1 in addition to IL-2. Gamma irradiation of APC from young MRL/Mp-lpr/lpr mice or treatment of APC with a mAb (J11D) and C, completely abrogated their stimulatory capacity. These experiments suggest that B cells are the predominant APC responsible in the activation of autoreactive T cells in MRL/Mp-lpr/lpr mice. Lymph node cells from C57BL/6-lpr/lpr or C3H-lpr/lpr mice were unable to spontaneously proliferate or produce IL-2. Lymph node cells from (MRL/Mp-lpr/lpr x C57BL/6-lpr/lpr) F1 mice or (C3H-lpr/lpr x MRL/Mp-lpr/lpr) F1 mice did proliferate and produced IL-2 after in vitro culture. Using T cells from these F1 animals and APC from each parental haplotype, we found that APC from MRL/Mp-lpr/lpr mice induced more proliferation and greater amounts of IL-2, when compared to APC from F1 animals. APC from C57BL6-lpr/lpr mice or C3H-lpr/lpr were unable to induce spontaneous proliferation and IL-2 production. Therefore, B cells from MRL/Mp-lpr/lpr mice appear to possess unique features that enable them to activate autoreactive T cells more effectively than B cells from other mice bearing the lpr/lpr gene.
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PMID:Autoreactive T cells in MRL/Mpr-lpr/lpr mice. Characterization of the lymphokines produced and analysis of antigen-presenting cells required. 313 46

A model of murine heterotopic allogeneic transplantation was used to study the rejection characteristics of three tissues--adult cornea, fetal pancreas, and fetal skin--for attributes that might explain their variation in rejection rates and help define the determinants of graft immunogenicity. Under identical conditions, tissues were transplanted to the renal subcapsular space and their base-line rejection rates compared. The expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1), was determined for each tissue, as was their ability to produce interleukin-6, IL-3, interferon-gamma, and granulocyte-macrophage colony-stimulating factor in vitro. These studies were performed under basal conditions and after stimulation with concanavalin A-stimulated spleen cell supernatant (CAS) or INF gamma. Corneal grafts had a slow rejection rate compared with pancreas and skin. While all three tissues had low basal expression of MHC class II, both fetal skin and pancreas, but not adult cornea, were able to increase this under our experimental conditions. Pancreas and skin produced IL-6 under basal conditions and could be stimulated to increase production 2-3-fold but the cornea did not basally produce IL-6 and showed minimal upregulation. We postulate that delayed corneal rejection, compared with pancreas and skin, results from two compounding deficiencies: the relative lack of class II MHC-positive APC and the inability to overcome this deficiency by upregulating class II expression and producing accessory molecules for antigen presentation.
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PMID:A comparison of corneal, pancreas, and skin grafts in mice. A study of the determinants of tissue immunogenicity. 751 13

Polymorphonuclear neutrophils (PMN) have long been thought to be short-lived, terminally differentiated cells incapable of synthesizing significant levels of protein, with their primary function being phagocytosis and the release of cytotoxic compounds. More recently, it has been demonstrated that PMN can produce a number of functionally diverse substances, including IL-1, IL-6, and IL-8. Although PMN express class I MHC Ag, it has not been definitely demonstrated that they can synthesize and express class II Ag. This would suggest that, although PMN can indirectly assist in the induction of an immune response through production of cytokines, they are incapable of acting as APC for CD4+ Th cells. We show that, in the presence of a defined medium (AIM V), human serum, and granulocyte-CSF, nearly 100% of isolated PMN can survive for up to 2 days in vitro. We also show that PMN express MHC class II when present as bystander cells in a monocyte/T cell Ag presentation assay for 44 h. In addition, granulocyte/macrophage CSF (GM-CSF), IFN-gamma, and IL-3 can induce class II on pure cultures of PMN, with GM-CSF appearing to be the most potent of the three cytokines. Furthermore, induction of class II on PMN is distinctly donor dependent, with PMN from some donors repeatedly showing very high, and others very low, induction of class II when treated with GM-CSF. Their potential to express class II suggests that PMN could play a significant role in immunoregulation and disease pathogenesis. The variation in class II induction on PMN from individual donors might explain previous failures to detect class II induction on PMN and could be a factor in the varied susceptibility of different individuals to autoimmune and inflammatory disorders such as the production of antibodies to PMN cytoplasmic components.
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PMID:Induction of MHC class II on human polymorphonuclear neutrophils by granulocyte/macrophage colony-stimulating factor, IFN-gamma, and IL-3. 833 42

T blasts of six established human CD4+ T cell clones with defined Ag specificity and cytokine secretion profile (3 Th1 and 3 Th2) were immortalized with Herpesvirus saimiri (HVS) and compared with their uninfected counterparts for their ability to proliferate, produce cytokines, and express cytolytic activity. HVS-transformed Th1 and Th2 clones neither substantially changed their original surface markers nor lose their ability to proliferate in response to their specific Ag but did acquire the ability to proliferate in response to contact signals delivered by SRBC or autologous APC alone. In addition, transformation by HVS substantially enhanced the lectin-dependent cytolytic activity of Th1 clones and enabled noncytolytic Th2 clones to exert cytolytic activity. HVS-transformed Th1 clones but not their uninfected counterparts spontaneously transcribed and secreted Th1-type cytokines (IL-2, IFN-gamma, and TNF-beta) and such a production was further enhanced by stimulation with either SRBC or PMA plus anti-CD3 mAb. HVS transformed but not uninfected Th2 clones constitutively expressed both IL-4 and IL-2 mRNA and secreted IFN-gamma. Stimulation with PMA plus anti-CD3 mAb induced uninfected Th2 clones to secrete high amounts of IL-4 and IL-5 but not Th1-type cytokines, whereas the same HVS-transformed Th2 showed minimal IL-4 and IL-5 secretion with concomitant high production of IL-2, IFN-gamma, and TNF-beta. Transformation by HVS also resulted in up-regulation of TNF-alpha and IL-3 production by both Th1 and Th2 clones. The ongoing proliferation of HVS-transformed clones was partially inhibited by either anti-IL-2 or anti-IL-3 antibodies and virtually abolished by the combined addition of the two anticytokine antibodies, suggesting that both IL-2 and IL-3 can function as autocrine growth factors for HVS-transformed Th1 and Th2 clones.
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PMID:Immortalization with herpesvirus saimiri modulates the cytokine secretion profile of established Th1 and Th2 human T cell clones. 840 53

PGE2 is an immunomodulator that selectively inhibits the production of lymphokines associated with Th1 cells (IL-2 and IFN-gamma) but not Th2 cells (IL-4 and IL-5). We examined the effect of PGE2 on the production of IL-3 and granulocyte-macrophage (GM)-CSF from murine Th1 and Th2 clones. When the T cells were stimulated with Ag and APC, PGE2 inhibited IL-3/GM-CSF production from 3 Th1 clones and 1 Th2 clone, but enhanced production from 3 Th2 clones. A more specific bioassay demonstrated that IL-3 production was differentially affected by PGE2 in the Th clones. These data suggested that the effect of PGE2 on IL-3 production is dependent, not on a property of the lymphokine, but on a property of the T cell. The responsiveness to PGE2 did not consistently differ between Th1 and Th2 cells, and the observed heterogeneity in the response of Th2 clones did not correlate with the ability to induce increases in intracellular [Ca2+]. However, we postulated that signaling differences between the clones might explain the varied responsiveness to PGE2. If so, then the mode of stimulation might be expected to activate different pathways and thus affect the PGE2-responsiveness. Stimulation with ionomycin induced variable levels of IL-3/GM-CSF from the T cell clones. APC-derived costimulation dramatically enhanced IL-3/GM-CSF; the cells which produced high levels in response to ionomycin alone were not detectably costimulating each other. Interestingly, PGE2 enhanced IL-3/GM-CSF (and IL-3 alone in at least some cases) from cells stimulated with ionomycin alone, demonstrating that the mode of stimulation affects the PGE2-responsiveness. Addition of APC not only enhanced lymphokine production, but also altered the PGE2-responsiveness of the Th1 cells. In these cells, PGE2 either inhibited IL-3 and GM-CSF production or had no effect, in no case was the lymphokine production enhanced by PGE2 as it had been with ionomycin alone. These data indicate that the presence of APC-derived costimulatory signals can alter the effect of PGE2 on Th cell lymphokine production.
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PMID:Effect of prostaglandin E2 (PGE2) on IL-3/granulocyte-macrophage colony-stimulating factor production by T helper cells. Mode of stimulation and presence of costimulation can determine response to PGE2. 843 11

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