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)

Experimentally induced and naturally occurring inflammatory diseases of the central nervous system (CNS) are often associated with a breakdown of the blood-brain barrier and edema within the CNS itself. CD4+ T cells are now clearly implicated in the pathogenesis of the induced CNS disease, experimental autoimmune encephalomyelitis, and previous in vivo experiments had indicated that these cells may be capable of directly damaging the CNS vasculature. To assess the capacity of CD4+ T cells to damage brain vascular endothelial cells (EC) in vitro, two lines with specificity for myelin basic protein and OVA were prepared and added to cultures of EC. We show here that both lines, when added in a resting state, severely disrupt the EC monolayers in an Ag-specific manner. The interaction is dependent on the recognition of Ag in the context of MHC class II and is blocked in the presence of mAb specific for CD4. Addition of T cell lines preactivated on irradiated thymocyte APC caused a high level of Ag nonspecific damage to the EC, which was not blocked by the addition of anti-CD4 mAb. Supernatants derived from these latter cells did not alone damage the EC monolayers despite the presence of TNF activity suggesting that T cell-EC contact may be required for these cell lines to mediate their effector function. Both resting and preactivated lines adhered strongly to the EC in the absence of Ag. The capacity of CD4+ T cells to strongly adhere to, and disrupt the integrity of, brain vascular EC may be important in the early stages of CNS disease mediated by this cell type.
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PMID:Antigen-specific damage to brain vascular endothelial cells mediated by encephalitogenic and nonencephalitogenic CD4+ T cell lines in vitro. 169 55

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

During the past decade, much has been learned about the pathophysiology of ACH--yet much remains to be determined. Although LC, IL-1, IL-2, IFN-gamma, and the T effector circuits have been extensively studied, it is still not clear whether it is LC- or keratinocyte-derived IL-1 that is crucial in ACH, whether IL-1 acts primarily on T-cells or the APC, whether other cytokines are involved in the circuit (TNF, KTGF?), the exact relationships between T effector, T memory, and other T helper cells, what the functions of mast cells and basophils are in the allergic reaction, and how the regulatory circuits (including prostaglandins and eicosanoids) affect the outcome of ACH. The mechanism of suppression remains even less well understood despite the potential application of this knowledge to the treatment of diseases caused by Type IV hypersensitivity. A better understanding of the ACH mechanism will lead not only to more sophisticated ACH treatment, but also to a better understanding of the cell-mediated events of cutaneous viral replication, organ transplantation, and tumor growth.
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PMID:The pathophysiology of allergic contact hypersensitivity. 269 Oct 41

The growth-inhibitory activity of recombinant human tumor necrosis factor (rH-TNF: PAC-4D) against 32 human cultured cell lines derived from leukemias and lymphomas (7 T cell, 11 B cell, 5 non-T,non-B cell and 9 myeloid cell lines) was measured quantitatively by in vitro regrowth assay. The growth of two non-T,non-B-cell lines (Reh, P30/OHK) and six myeloid cell lines (ML-1, U937, THP-1-0, P31/FUJ, P39/TSU, HEL) was found to be significantly inhibited by a 72 hr treatment with PAC-4D. Although the levels of sensitivity of these cell lines to PAC-4D were different, it was common to all these cell lines that increasing the dose of PAC-4D did not augment the growth-inhibitory action above a certain level. Neither dose-dependent nor time-dependent growth-inhibitory action was observed, namely, exposure to 100 U/ml of PAC-4D for 48 hr was sufficient to exhibit maximum growth-inhibitory action. Furthermore U937 cells were found to become completely resistant to PAC-4D during a continuous 12-day exposure to it. This resistance, however, was lost on culture of the cells with PAC-4D-free growth medium for 15 days. These results suggested that some non-T,non-B acute lymphoblastic leukemias and acute myelogenous leukemias might show an initial response to PAC-4D therapy, but prolonged administration might induce resistance to PAC-4D rather than increase the anti-tumor effect.
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PMID:Potential limitation of growth-inhibitory action of recombinant human tumor necrosis factor (PAC-4D) due to easy induction of resistance: evidence in vitro. 282 76

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

The antitumor effects of human recombinant TNF (PAC-4D) were examined on three human gynecological carcinomas transplanted into CD-1 nude mice (uterine cervical carcinoma: UZ-1-N; ovarian carcinoma: OCl-1-N and OS-4-N). PAC-4D was administered intratumorally at a dose of 1,000 U, 3,000 U or 10,000 U/head from day 0 to day 4. Tumor size, body weight and peripheral WBC were measured on days 0, 4, 8, 12 and 16 and histological studies were made on day 6. The results were as follows: With UZ-1-N, intratumoral administration of PAC-4D at doses of 3,000 U and 10,000 U/head caused a marked inhibition of the tumor growth. Similarly, antitumor activity of PAC-4D against OCl-1-N was remarkable at a dose of 10,000 U/head. The administration of PAC-4D at doses of 3,000 U and 10,000 U/head was not effective against OS-4-N. The histological changes of grade II A-B by Ohboshi-Shimosato criteria of response were observed in the tumor of the effective groups against PAC-4D. There were no influences on the body weight and WBC after administration of PAC-4D. Although tumor cells possessed different sensitivities to PAC-4D, PAC-4D is strongly recommended for the treatment of gynecological malignancies.
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PMID:[Antitumor effects of the tumor necrosis factor (PAC-4D) against human gynecological carcinoma transplanted into nude mice]. 360 53

The bacterial superantigen staphylococcal enterotoxin B (SEB) induces in vivo a state of anergy defined by the inability of V beta 8+ CD4+ T cells to produce IL-2 upon restimulation in vitro. However, restimulation in vivo triggers a burst of acutely released lymphokines including IL-2 and TNF, paralleled by up-regulation of lymphokine-specific mRNA. Since anergy as defined in vitro appears not to operate in vivo, we analyzed parameters able to induce responsiveness in anergic T cells. We show here that in vitro stimulation of anergic T cells with competent Ag-presenting cells induces responsiveness, provided the APC (activated B cells or dendritic cells) present high concentrations of SEB. Crosslinking of CD28 molecules on anergic T cells could substitute the requirement for competent APC. Quantitation of TCR threshold by determining the SEB concentrations able to trigger half-maximal T cell responses revealed that anergic and normal T cells exhibited the same TCR threshold for the expression of functional IL-2 receptors (IL-2R), yet the TCR threshold for induction of IL-2 production was 10- to 100-fold elevated in anergic T cells. TCR threshold for normal and anergic T cells was further dependent on the type of APC, i.e., costimulus-competent APC required 100-fold less SEB. The results indicate that extrinsic factors such as ligand concentration and costimulus competence of APC can overcome the heightened TCR threshold of anergic T cells, thus reverting anergy into responsiveness.
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PMID:Induction of responsiveness in superantigen-induced anergic T cells. Role of ligand density and costimulatory signals. 760 25

CD4+ T cell clones were generated to tetanus toxin or to two tetanus toxin-derived peptides p2 (AA 830-834) and p30 (AA 947-976). 11 of the 24 p30-specific clones reacted to shorter p30 subunits (p301 or p302), and only 14 of the p2 or p30-specific clones reacted with TT presented by EBV-transformed B cell lines (B-LCL). The p30-specific clones were HLA-DP4 restricted. In contrast to autologous B cell lines, the majority of allogeneic, but HLA-DP4-positive cell lines failed to present p30 to the specific clones. We concluded that T cell clones are highly specific and that both, small alterations of the peptide length as well as discrete differences of the HLA-molecule may abrogate recognition of the peptide HLA complex by T cells. Moreover, use of peptides as stimulators of T cells may recruit and activate T cells which fail the "original" peptide, derived from normal antigen processing. Clones could usually be maintained in culture for 4-6 months, but with the help of freezing and thawing some clones are now available for over 2 years and still specific. Comparison of different autologous antigen-presenting cells, namely B-LCL and activated MHC class II-positive T cells revealed that not all clones were able to mount a proliferative response to peptide presentation by T cells, while all clones proliferated to B cells as APC. If stimulated with peptide and B-LCL, the clone proliferating to T cells as APC (so-called T responder clones) secreted a broad spectrum of cytokines (Th0-like) and were easier to maintain in culture. In contrast, clones which were unable to proliferate to peptide presentation, so-called T-nonresponder clones, showed a more restricted cytokine pattern and elevated or very low IL4/IFN gamma ratio upon antigen specific stimulation. However, all clones secreted at least small amounts of IL2, IL4, IFN gamma and TNF alpha, if stimulated by PMA and ionomycin. Thus, both chemical and antigen-specific stimulations should be considered if T cell clones are classified as Th1 or Th2, whereby those clones, which secrete a limited cytokine pattern after antigen stimulation only, might be named Th1 or Th2 like clones, while clones which even after PMA/ionomycin do not secrete all cytokines, might represent "real" Th1 or Th2 clones.
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PMID:Peptide-induced T cell clones: specificity, MHC restriction, proliferation and cytokine pattern as a function of different stimulations. 787 53

Molecules of the TNF-R family have been shown to be essential in the regulation of lymphocyte growth and differentiation. The TNF-R family member CD27 binds to a type II transmembrane molecule belonging to the TNF gene family (CD27L) that is identical to the lymphocyte activation Ag CD70. Using transfected mouse fibroblasts expressing human CD70, we demonstrate here that interaction of CD27 with its ligand provides a potent second signal for cytokine production, induction of activation Ags, and proliferation of unprimed CD45RA+, and to a lesser extent, of primed CD45R0+ peripheral blood T cells. In contrast to costimulatory signals delivered via the CD28-ligand B7-1 (CD80), CD70 was found to induce relatively low IL-2, IL-4, and IL-10 but comparable TNF-alpha secretion. Proliferation of CD45RA+, but not of CD45R0+ T cells, was found to be largely resistant to blocking of IL-2/IL-2R interaction. Finally, the finding that CD70 and CD80 cooperate in the induction of T cell proliferation indicates that cooperation of both molecules may be essential for optimal T cell stimulation. The interaction between CD27 and its ligand CD70 might be of particular importance for the recruitment of T cells from the unprimed T cell pool. Moreover, as CD70 expression in vivo is confined to activated B and T lymphocytes, only a limited set of APC are able to generate this specific second signal for T cell expansion.
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PMID:Engagement of CD27 with its ligand CD70 provides a second signal for T cell activation. 787 36

Monocyte phenotype heterogeneity is often associated with functional differences between the distinguished Mphi subpopulations. We have previously demonstrated that the Mphi subpopulation separated and stimulated by rosetting Mphi via the Type I Fc gamma R (CD64) are poor antigen presenting cells but can be induced to greater production of TNF alpha, IL-6 and PGE2 than the Fc gamma RI- Mphi population. Here we demonstrate that the Fc gamma RI- Mphi represent the major antigen presenting Mphi population and that APC capacity of the FcRI- Mphi can be further increased by elevating intracellular cAMP levels. Treatment of the Fc gamma RI+ Mphi with db cAMP decreases both their expression of CD64 and their capacity to produce TNF alpha to the levels typical of Fc gamma RI- Mphi. Db cAMP treatment of the Fc gamma RI+ Mphi subpopulation, however, cannot augment the antigen presenting capacity of this low APC Mphi subpopulation to the level of that of the Fc gamma RI- Mphi. Basal expression of the Mo3 activation marker was comparable in the FcRI+/FcRI- Mphi subpopulations, but the FcRI+ Mphi were induced by db cAMP treatment to increase their Mo3 expression to higher levels than the FcRI- Mphi. These results suggest that although elevated intracellular cAMP levels can modulate some Fc gamma RI+ Mphi functions to more closely parallel those of the Fc gamma RI- Mphi, this treatment cannot increase the efficiency of the Fc gamma RI+ Mphi subpopulation as an antigen presenting cell.
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PMID:Dibutyryl-cAMP modulation of receptor expression and antigen presentation capacity in monocyte subpopulations. 818 3


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