Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subcutaneous immunization with the thymus independent Ag, TNP-Ficoll, does not elicit plaque-forming cell response from the regional lymph node B cells even though a good response is obtained with the splenic B cells. Lymph node cells respond well to the thymus independent 1 Ag, TNP-Brucella abortus. Because TNP-Ficoll is a soluble Ag and may not be retained well in the lymph nodes, we emulsified it with Freund's adjuvant and injected it into foot pads. This did not result in any antibody response in the popliteal and inguinal lymph nodes though once again splenic B cells gave excellent responses. We find that the in vivo response to TNP-Ficoll can be induced in the lymph node if TNP-Ficoll is injected along with B. abortus in the foot pads of normal mice. This observation could not be repeated in the splenectomized mice implicating the role of the migration of APC or B cells from spleen to lymph nodes. Similar differential responses are obtained from lymph node and splenic B cells in the in vitro cultures. Lymph node cells respond to TNP-Ficoll with the addition of normal irradiated spleen cells but not with Sephadex G-10-passed spleen cells. This shows the absence of APC or lymphokines which stimulate B lymphocytes to respond to TNP-Ficoll in the lymph nodes. We found that IL-1 but not IL-2 or IL-4 was able to induce TNP-Ficoll response from the lymph node B cells.
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PMID:Differential responses of B cells from the spleen and lymph node to TNP-Ficoll. 312 3

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

Although the precise mechanism of action of cyclosporine (CS) is unknown, there is substantial evidence that CS preferentially acts on T cells by impairing lymphokine production. Recent studies have demonstrated that CS may also inhibit the functions of accessory cells and APC. Since topically applied CS inhibits contact sensitivity and epidermal Langerhans cells (LC) are very effective accessory cells and APC, we determined whether CS directly affects their accessory cell functions. Murine LC were pulsed with solvent control or with various doses of CS (up to 10 micrograms/ml) and then Con A-induced T cell proliferation was assayed. CS pulsing of LC caused, when compared with solvent control-pulsed LC, a dose-dependent decrease in T cell stimulation (up to 93%). LC fixed with paraformaldehyde after 2-h CS pulsing showed a similar degree of decreased accessory cell function, indicating that the immunosuppressive action is established by 2 h. The inhibitory capacity of CS pulsing on LC is not likely to be related to diminished IL-1 production, enhanced PG biosynthesis, or decreased surface Ia Ag intensity. The possibility of carryover of CS into the culture supernatants was ruled out by adding CS-pulsed LC or their supernatants to other T cell proliferative assays. Thus, these studies indicate that CS directly inhibits accessory cell functions of LC.
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PMID:The effect of cyclosporine on epidermal cells. I. Cyclosporine inhibits accessory cell functions of epidermal Langerhans cells in vitro. 325 8

A murine cloned Th cell line specific for the antigen conalbumin in the context of self I-A molecules can be activated by low concentrations of soluble antireceptor mAb. By using an antireceptor mAb to shared antigenic determinants on T cell receptors, we have shown that the ability to be activated by soluble antireceptor mAb is an unusual, although not unique, feature of this cloned T cell line. This activation does not involve occult APC, FcR, or interaction between individual cloned T cells, as limiting-dilution analysis shows that individual cells of this clone will grow in the presence of the antireceptor antibody and IL-1 as stimulus. This cloned T cell line is highly immunogenic in vivo, giving rise to antireceptor antibodies that stimulate its growth in both mice and rats. This response is not dependent upon exogenous T cells. Rather, the clone directly interacts with complementary B cells, as shown by the production of mAb in nude mice, and by production of stimulating antireceptor antibodies by purified B cells cultured with cloned Th cells in vitro. Several features of this cloned Th cell line, most especially its ability to be activated, rather than inhibited, by antireceptor antibodies, may account for its striking ability to directly activate B cells bearing complementary receptors. The direct interaction of the cloned Th cell with B cells bearing complementary receptors may serve as a model for receptor-receptor interactions in the generation of both T and B cell repertoires.
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PMID:Direct interactions between B and T lymphocytes bearing complementary receptors. 348 11

T cell activation is widely believed to depend on interleukin 1 (IL 1) provided by antigen (Ag)-presenting cells (APC). Because IL 1 is not a constitutive product of APC, we examined the features of its production during the interaction of murine T cell clones and APC. We observed that IL 1 was detectable in supernatants of most myoglobin-specific T cell clones grown with APC and Ag. Two of these T cell clones induced exceptionally high levels of IL 1 in their supernatants, and these same clones demonstrated the unusual restriction to I-Ek, which is a low responder type for sperm whale myoglobin. One of these clones was characterized additionally as to the mechanism of IL 1 induction. This clone rapidly stimulated IL 1 production in the APC population (detectable at 4 hr of co-culture) or in macrophages (M phi) or a M phi-like cell line. IL 1 induction was Ag dependent and H-2 restricted. Induction was radioresistant, both on the part of the T cell and of the IL 1 producer. The IL 1-induction process was attributable to a lymphokine produced by the T cell clone. This lymphokine was distinct from IFN-gamma, TNF and CSF-1 and may account for a principal mechanism of T----APC signalling. The induced IL 1 was the same in size, co-mitogenicity, and pyrogenicity as lipopolysaccharide-induced IL 1.
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PMID:IL 1 induction by murine T cell clones: detection of an IL 1-inducing lymphokine. 349 59

In order to clarify the nature of the defect in the process of antigen presentation caused by uv radiation, low-density spleen cells were used as a potent APC source in a hapten-specific cytolytic T-cell (Tc) system. It was demonstrated that IA+ weakly adherent low-density spleen cells, when directly coupled with azobenzene arsonate (ABA), led to the activation ABA-specific Tc. When these APC were exposed to uv radiation (12 J/m2/sec) for 30 sec, their ability to lead to Tc activation was markedly inhibited. The defect imposed by uv radiation could be specifically bypassed by the addition of small amounts of homogeneous IL-1 or IL-2. This led to the specific activation of ABA-reactive H-2-restricted Tc. The purified IL-1 was also found to bypass the systemic defect imposed in vivo by external uv radiation of mice. This may indicate a potential therapeutic role for IL-1.
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PMID:Molecular signals in antigen presentation. I. Effects of interleukin 1 and 2 on radiation-treated antigen-presenting cells in vivo and in vitro. 660 25

Murine low-density spleen cells have potent antigen-presenting ability in a hapten-specific cytolytic T lymphocyte (CTL) system using the hapten azobenzenearsonate (ABA). Exposure of these cells to 0.33 KJ/m2 of ultraviolet radiation (UVR) after coupling to hapten results in markedly inhibited antigen-presenting function that can be substantially corrected or bypassed by interleukin 1 (IL 1). These results have been interpreted to reflect an inhibition of Lyt-1+ T cell activation by UVR-treated APC. Treatment of these cells sequentially with 1500 rad of gamma-radiation (GR) prior to hapten coupling, followed by 0.33 KJ/m2 of UVR radiation after coupling, results in an antigen-presenting defect only minimally improved by IL 1. However, partially purified interleukin 2 (IL 2) can completely bypass or correct this defect. Thus, combined GR and UVR induces a different or more profound defect in APC function when compared to UVR alone. However, these cells do provide a signal(s) other than hapten necessary for CTL activation because ABA-coupled high density spleen cells do not activate CTL cells, even with the addition of IL 2. Fluorescence-activated cell sorter analysis demonstrates that exposure of these low density spleen cells to GR or UVR results in decreased I-A antigen expression at 24 hr than either alone. The addition of nonhapten-coupled low-density APC partially reconstitutes the ability of combined GR/UVR-treated LD-APC to present antigen, and this effect is enhanced by the administration of exogenous IL 1. This occurs despite a lack of significant accessory cell activity by the LD-APC for the ABA hapten, and indicates that combined GR/UVR-treatment of APC is not functionally equivalent to completely removing them.
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PMID:Molecular signals in antigen presentation. II. Activation of cytolytic cells in vitro after ultraviolet radiation or combined gamma and ultraviolet radiation treatment of antigen-presenting cells. 660 92

Although superantigens and their molecular interactions with MHC class II molecules have been well characterized recently, little is known concerning the physiological function of different types of APC in inducing superantigen-mediated T cell activation. To evaluate the potential of nonhematopoetic cells to present superantigens to T cells, we have tested astrocytes as a typical "nonprofessional" APC. Although astrocytes can express appropriate levels of MHC class II products and adhesion molecules, they turned out to be unable to mediate superantigen-driven activation of normal T lymphocytes, even in the presence of rather high concentrations of toxins. In contrast, they could properly present equimolar amounts of nominal Ag to various Ag-specific T cell lines under the same experimental conditions. Inability of astrocytes to support T cell responses to superantigens could not be overcome by addition of cytokines IL-1 and IL-6. Binding studies with class II-expressing astrocytes revealed that T cell unresponsiveness was not due to a general failure of astrocytes to bind the superantigen. Moreover, the resulting SA-class II complex was recognizable by TCR, as demonstrated by the capacity to activate IL-2 secretion in T cell hybridomas. Our results extend previous studies demonstrating marked differences of various types of APC to trigger T cell responses to superantigens and describe for the first time a dissociation of the Ag-presenting capacity for peptide-Ag vs superantigen on an accessory cell.
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PMID:Dissociation of antigen-presenting capacity of astrocytes for peptide-antigens versus superantigens. 767 36

Purified CD4+ T cells require TCR engagement and Ag-nonspecific co-stimulatory signals to produce IL-2 and proliferate. A number of recent studies have demonstrated that the interaction of the B7 molecule expressed on APC with the T cell-associated CD28 molecule provides a potent co-stimulatory signal to both freshly isolated CD4+ T cells and cloned Th1 cells. Earlier reports have described the role of cytokines, in particular IL-6 and IL-1, as costimulatory molecules for T cell activation. We previously reported that IL-6 and IL-1 synergize to co-stimulate proliferation of purified mouse CD4+ T cells in conjunction with anti-TCR mAb. In this report we explore the interaction of IL-6, IL-1, and CD28 signaling in the activation of mouse CD4+ T cells, and demonstrate that the co-stimulatory requirements of the cells vary depending on the mode of TCR stimulation. CD28 signaling is not sufficient to co-stimulate responses of high buoyant density CD4+ T cells to anti-TCR-conjugated agarose beads; there is an additional requirement that can be supplied by exogenous IL-6 but not by IL-1. In contrast, in responses to anti-TCR mAb that is passively bound to the bottom of culture wells, CD28 stimulation is sufficient to co-stimulate proliferation, resulting in a very high level of IL-2 production; there is no additional requirement for exogenous IL-6 or IL-1. Possible explanations for the differential requirement for IL-6 in the two systems are discussed. Our results are consistent with the notion that CD28 signaling plays a central role in co-stimulating T cell responses. However, the results also suggest that, depending on the nature of the TCR stimulus, T cell activation may also require additional co-stimulatory signals provided by cytokines.
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PMID:Role of IL-6, IL-1, and CD28 signaling in responses of mouse CD4+ T cells to immobilized anti-TCR monoclonal antibody. 790 3

In these experiments, effects of IL-12 on the proliferation and IL-2R expression of Th1 and Th2 clones were studied. Although neither Th1 nor Th2 clones proliferated on an Ag stimulation with B cell APC, Th1 clones but not Th2 clones, exhibited IL-2-dependent proliferation in the presence of IL-12 in response to the Ag stimulation. The IL-2R alpha-chain was also shown to be induced on Th1 clones when they were stimulated with B cell APC in the presence of IL-12. Effects of IL-12 on these T cell functions were indicated to be exerted in concert with IL-2, although IL-12 did not enhance IL-2 production of Th1 clones. Cytokines produced by Th1 clones such as IFN-gamma and TNF-alpha were indicated not to be involved in induction of the IL-2R alpha-chain expression or proliferation. IL-12 also induced proliferation and IL-2R alpha-chain expression of Th1 clone stimulated with anti-CD3 in the absence of APC, indicating that IL-12 exerted the effect on Th1 cells directly and other costimulator signal from APC is not required for the function of IL-12. In contrast to IL-12, IL-1 induced proliferation and IL-2R alpha-chain expression of Th2 clones stimulated with Ag on B cell APC. The failure of IL-12 in the induction of IL-2R alpha-chain expression on Th2 clone seemed not to be caused by the IL-4 produced by the clone. These results suggest that IL-12 plays an important role in IL-2R alpha-chain expression and proliferation of Th1 clones, but not Th2 clones, as a second signal.
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PMID:Second signal activity of IL-12 on the proliferation and IL-2R expression of T helper cell-1 clone. 790 27


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