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)

Three HSV type 1 (HSV-1) and HSV type 2 (HSV-2) common ("HSV-type common") and three HSV-1 specific CTL clones, which were CD3+, CD4+, CD8-, 4B4+, and 2H4-, were established. These clones proliferated in response to stimulation with HSV in the presence of autologous APC. The HSV type specificity of the proliferative response was identical with that of the cytotoxic activity of the clones. The cytotoxic activity and the proliferative response were both inhibited by addition of anti-HLA-DR mAb to the culture. After culture of these CTL clones with autologous B cells and macrophages followed by HSV Ag stimulation, anti-HSV antibody was detected in the culture supernatant. The HSV type specificity of the helper function for antibody production was identical with that of the cytotoxicity, i.e., HSV-type common clones, upon stimulation with either HSV-1, or HSV-2, and HSV-1-specific clones, upon stimulation with HSV-1 but not with HSV-2, showed helper activity for anti-HSV antibody production by autologous B cells. Moreover, it was found that these clones produced humoral factors which help autologous B cells to produce antibody. The helper factors were produced by T cell clones in an HSV-type-specific manner. These data suggest that some CD4+ T cells can simultaneously manifest both specific cytotoxicity and helper activity for Ag-specific antibody production by B cells, and that these multifunctional T cells might play an important role in protection against viral infection.
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PMID:Helper activity in antigen-specific antibody production mediated by CD4+ human cytotoxic T cell clones directed against herpes simplex virus. 245 88

A cDNA encoding a form of hen egg lysozyme (HEL) lacking a leader sequence and predicted to be localized in the cytoplasm, was transfected into MHC class II-positive B lymphoma cells. Cytoplasmically expressed HEL (cytHEL) had a half-life of less than 5 min and did not react with HEL specific mAb suggesting non-native conformation. Cells expressing cytoplasmic HEL, as well as cells previously reported to express a low level of HEL retained in the endoplasmic reticulum (ERHEL), constitutively presented the HEL determinant encoded by residues 46-61 to a sensitive class II-restricted T hybridoma (3A9). Constitutive presentation of HEL determinants was not detectable in cytHEL or ERHEL transfectants using T hybridomas with lower sensitivity to exogenous Ag. Constitutive presentation of HEL46-61 derived from cytoplasmic HEL was demonstrable in multiple transfected clones and was most obvious when a CMV rather than SV40 promoter was used to express the cytHEL gene. The presentation of HEL46-61 by cytHEL transfectants was not due to HEL reuptake by bystander cells because there was no biochemical evidence of cytHEL shedding and cytHEL supernatants added to indicator APC did not result in HEL46-61 presentation. Constitutive presentation of endogenous HEL46-61 by the cytHEL and ERHEL transfectants was inhibited by chloroquine, and recovery of presentation of endogenous HEL was slower in cytHEL compared with ERHEL transfectants. The findings indicate that class II-restricted presentation of Ag retained in the cytoplasm or endoplasmic reticulum does take place but probably requires abundant levels of intracellular Ag and is easily disrupted by lysosomotropic agents. These pathways of presentation may be important when high levels of foreign endoplasmic reticulum-retained or cytoplasmic Ag are present (e.g., viral infection), and during the acquisition of self-tolerance by highly sensitive developing T cells.
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PMID:Class II-restricted presentation of a hen egg lysozyme determinant derived from endogenous antigen sequestered in the cytoplasm or endoplasmic reticulum of the antigen presenting cells. 847 26

Substantial progress has been made in understanding Ag presentation to T cells; however, relatively little is known about the location and frequency of cells presenting viral Ags during a viral infection. Here, we took advantage of a highly sensitive system using lacZ-inducible T cell hybridomas to enumerate APCs during the course of respiratory Sendai virus infection in mice. Using lacZ-inducible T cell hybridomas specific for the immunodominant hemagglutinin-neuraminidase HN421-436/I-Ab and nucleoprotein NP324-332/Kb epitopes, we detected APCs in draining mediastinal lymph nodes (MLNs), in cervical lymph nodes, and also in the spleen. HN421-436/I-Ab- and NP324-332/Kb-presenting cells were readily detectable between days 3 and 9 postinfection, with more APCs present in the MLN than in the cervical lymph nodes. Interestingly, no infectious virus was detected in lymphoid tissue beyond day 6, suggesting that a depot of noninfectious viral Ag survives, in some form, for 2-3 days after viral clearance. Fractionation of the MLN demonstrated that APC frequency was enriched in dendritic cells and macrophages but depleted in the B cell population, suggesting that B cells do not form a large population of APCs during the primary response to this virus.
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PMID:Enumeration of antigen-presenting cells in mice infected with Sendai virus. 1009 89

Ag-specific CTL can protect against tumors and some viral infections and may be useful for adoptive immunotherapy. Here, we show that purified CD8+ T cells from naive C57BL/6 mice can be primed in vitro with different immunogenic peptides, which bind to MHC class I gene products, and IL-2 to exhibit specific and MHC-restricted effector function in vitro and in vivo protection against lymphocytic choriomeningitis virus infection and B16.F10 melanoma lung metastases. Limiting dilution assays in the absence of feeder cells with highly purified CD8+ T cells from two transgenic mice strains, each expressing a different MHC class I-restricted TCR, indicated that only peptide and IL-2, but not TCR- cells, were required for the growth of naive CD8+ T cells. These alternative minimal requirements for the activation and expansion of specific CD8+ T lymphocytes, without the need for professional APC, may be exploited for adoptive immunotherapy.
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PMID:Protective immunity from naive CD8+ T cells activated in vitro with MHC class I binding immunogenic peptides and IL-2 in the absence of specialized APCs. 1038 32

Potent and readily accessible APC are critical for development of immunotherapy protocols to treat viral disease and cancer. We have shown that B lymphoblastoid cell lines (BLCL) that stably express CMV phosphoprotein 65 (BLCLpp65), as a result of retroviral transduction, can be used to generate ex vivo CTL cultures that possess cytotoxicity against CMV and EBV. In this report, we demonstrate that the EBV-specific cytotoxicity in the BLCLpp65-primed culture had a spectrum of EBV-Ag recognition similar to that of the BLCL-primed counterpart, suggesting that retroviral transduction and expression of the CMV Ag would not compromise the Ag-presenting capacity of BLCL. In addition, BLCLpp65 appeared to present multiple natural pp65 epitopes, because pp65-specific CTL, which recognized different CMV clinical isolates, were generated in BLCLpp65-primed cultures from individuals with various HLA backgrounds. Consistent with a polyclonal expansion of virus-specific CTL, T cell lines established from the BLCLpp65-primed CTL cultures expressed different TCR-Vbeta Although most of the virus-specific T cell isolates were CD8+, EBV-specific CD4+ lines were also established from BLCLpp65-primed cultures. Western blot analysis revealed that the CD8+ lines, but not the CD4+ line, expressed granzyme B, consistent with features of classic CTL. Thus, our results suggested that BLCL stably expressing a foreign Ag might be used as a practical APC to elicit CD8+ T cell responses.
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PMID:B lymphoblastoid cell lines as efficient APC to elicit CD8+ T cell responses against a cytomegalovirus antigen. 1103 22

IgA is considered to be the principal Ab involved in defense against pathogens in the mucosal compartment. Using mice with a targeted disruption in IgA gene expression (IgA(-/-) mice), we have examined the precise role of IgA in protective anti-influenza responses after intranasal vaccination. IgA(-/-) mice immunized intranasally with soluble hemagglutinin (hemagglutinin subtype 1) and neuraminidase (neuraminidase subtype 1) vaccine in the absence of adjuvant were found to be more susceptible to influenza virus infection than IgA(+/+) mice (13 vs 75% survival after virus challenge). Inclusion of IL-12 during immunization restored the protective efficacy of the vaccine to that seen in IgA(+/+) animals. IgA(-/-) mice had no detectable IgA expression, but displayed enhanced serum and pulmonary IgM and IgG Ab levels after IL-12 treatment. Assessment of T cell function revealed markedly depressed splenic lymphoproliferative responses to PHA in IgA(-/-) animals compared with IgA(+/+) mice. Furthermore, IgA(-/-) animals displayed impaired T cell priming to the H1N1 subunit vaccine, with concomitant reduction in recall memory responses due to a defect in APC function. Collectively, these results provide evidence that a major role of IgA is to facilitate presentation of Ag to mucosal T cells. IL-12 treatment can overcome IgA deficiency by providing adequate T cell priming during vaccination.
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PMID:IgA immunodeficiency leads to inadequate Th cell priming and increased susceptibility to influenza virus infection. 1112 96

T lymphocytes play a decisive role in the course and clinical outcome of viral CNS infection. Summarizing the information presented in this review, the following sequence of events might occur during acute virus infection: After invasion of the host and a few initial rounds of replication, the virus reaches the CNS in most cases by hematogeneous spread. After passage through the BBB, CNS cells are infected and replication of virus in brain cells causes activation of the surrounding microglia population. Moreover, local production of IFN-alpha/beta induces expression of MHC antigens on CNS cells, and microglial cells start to phagocytose cellular debris, which accumulates as a result of virus-induced cytopathogenic effects. Upon phagocytosis, microglia becomes more activated; they up-regulate MHC molecules, acquire antigen presentation capabilities and secrete chemokines. This will initiate up-regulation of adhesion molecules on adjacent endothelial cells of the BBB. Transmigration of activated T lymphocytes through the BBB is followed by interaction with APC, presenting the appropriate peptides in the context of MHC antigens. It appears that CD8+ T lymphocytes are amongst the first mononuclear cells to arrive at the infected tissue. Without a doubt, their induction and attraction is deeply influenced by natural killer cells, which, after virus infection, secrete IFN-gamma, a cytokine that stimulates CD8+ T cells and diverts the immune response to a TH1-type CD4+ T cell-dominated response. Following the CD8+ T lymphocytes, tissue-penetrating, TH1 CD4+ T cells contact local APC. This results in a tremendous up-regulation of MHC molecules and secretion of more chemotactic and toxic substances. Consequently an increasing number of inflammatory cells, including macrophages/microglia and finally antibody-secreting plasma cells, are attracted to the site of virus infection. All trapped cells are mainly terminally differentiated cells that are going to enter apoptosis during or shortly after exerting their effector functions. The clinical consequences and the influence of the effector phase on the further course of the infection depends on the balance and fine-tuning of the contributing lymphoid cell populations. Generally, any delay in the recruitment of effector lymphocytes to the tissue or an unbalanced combination of lymphocyte subsets allows the virus to spread in the CNS, which in turn will cause severe immune-mediated tissue effects as well as disease. If either too late or partially deficient, the immune system response may contribute to a lethal outcome or cause autosensitization to brain-specific antigens by epitope spreading to the antigen-presenting system in peripheral lymphoid tissue. This could form the basis for subsequent booster reactions of autosensitized CD4+ T cells--a process that finally will end in an inflammatory autoimmune reaction, which in humans we call multiple sclerosis. In contrast, a rapid and specific local response in the brain tissue will result in efficient limitation of viral spread and thereby a subclinical immune system-mediated termination of the infection. After clearance of virus-infected cells, downsizing of the local response probably occurs via self-elimination of the contributing T cell populations and/or by so far unidentified signal pathways. However, much of this is highly speculative, and more data have to be collected to make decisive conclusions regarding this matter. Several strategies have been developed by viruses to escape T cell-mediated eradication, including interference with the MHC class I presentation pathway of the host cell or "hiding" in cells which lack MHC class I expression. This may result in life-long persistence of the virus in the brain, a state which probably is actively controlled by T lymphocytes. Under severe immunosuppression, however, reactivation of viral replication can occur, which is a lethal threat to the host.
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PMID:The role of T-cell-mediated mechanisms in virus infections of the nervous system. 1141 37

Theiler's murine encephalomyelitis virus induces immune-mediated demyelination in susceptible mice after intracerebral inoculation. A naturally occurring, low pathogenic Theiler's murine encephalomyelitis virus variant showed a single amino acid change within a predominant Th epitope from lysine to arginine at position 244 of VP1. This substitution is the only one present in the entire viral capsid proteins. In this paper, we demonstrate that the majority of T cells specific for VP1(233-250) and VP2(74-86) from wild-type virus-infected mice are Th1 type and these VP1-specific cells poorly recognize the variant VP1 epitope (VP1(K244R)) containing the substituted arginine. In contrast, the Th2-type T cell population specific for these epitopes predominates in variant virus-infected mice. Immunization with UV-inactivated virus or VP1 epitope peptides could not duplicate the preferential Th1/Th2 responses following viral infection. Interestingly, the major APC populations, such as dendritic cells and macrophages, produce IL-12 on exposure to the pathogenic wild-type virus, whereas they preferentially produce IL-10 in response to the low pathogenic variant virus. Thus, such a spontaneous mutant virus may have a profoundly different capability to induce Th-type responses via selective production of cytokines involved in T cell differentiation and the consequent pathogenicity of virally induced immune-mediated inflammatory diseases.
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PMID:Preferential induction of IL-10 in APC correlates with a switch from Th1 to Th2 response following infection with a low pathogenic variant of Theiler's virus. 1193 84

CD123(bright) plasmacytoid cells (PC) and CD1c(+) peripheral blood myeloid dendritic cells (DC) are two human DC precursors that can be expanded in vivo by Fms-like tyrosine kinase 3 ligand (FL). It has been proposed that PC and myeloid CD1c(+) DC may represent two distinct lineages of DC. However, the phylogenetic affiliation of PC and its relationship with myeloid DC remain controversial. Here we show that CD123(bright)HLA-DR(+) PC from FL-treated healthy volunteers can be divided into mutually exclusive subsets that harbor either lymphoid or myeloid features. Lymphoid-like PC represent the majority of PC and include pTalpha-, CD3epsilon-, and CD7-expressing cells. They exhibit TCR-beta gene loci in germline configuration and show low allostimulatory capacity, but produce type I IFN upon virus infection and can be differentiated in vitro into potent APC. Myeloid-like PC represent a minor fraction of the total PC population. They exhibit a striking PC/myeloid DC intermediate phenotype (CD5(+)CD11c(low)CD45RA(low)CD45RO(-)CD101(+)), produce proinflammatory cytokines, and do not require in vitro maturation to act as potent APCs. We propose that, rather than forming a lineage, PC might represent a population of lymphoid cells undergoing an in vivo cell fate conversion from a lymphoid to a myeloid cell type.
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PMID:CD123bright plasmacytoid predendritic cells: progenitors undergoing cell fate conversion? 1207 31

Respiratory viral infections have been shown to trigger exacerbations of asthma; however, the mechanism by which viral Th1-type inflammation exacerbates an allergic Th2-type disease remains unclear. We have previously shown that although adoptively transferred Th2 cells are inefficiently recruited to the lung in response to Ag, cotransfer of Th1 cells can increase accumulation of Th2 cells. In this study, we show that respiratory viral infection increases recruitment of resting Th2 cells specific for OVA even in the absence of OVA challenge. These findings suggest that the mechanism by which Th1-type inflammation enhances allergy is via an effect on recruitment. To study the role of the antigenic specificity of Th1 cells in the enhancement of Th2 cell recruitment and to determine whether virus-induced recruitment of OVA-specific Th2 cells may involve Th1 cells specific to a different Ag, we tested whether hen egg lysozyme-specific Th1 cells could synergize with OVA-specific Th2 cells. Challenge of mice that had received adoptively transferred Th1 cells plus Th2 cells induced the expression of inflammatory chemokines in the lung and increased both recruitment and activation of Th2 cells, leading to eosinophil recruitment, even in the absence of challenge with the Th2 Ag. Interestingly, as IL-5 supports eosinophilia, culture of resting Th2 cells with fresh APC induced production of IL-5 in the absence of specific Ag. Thus, Ag-specific activation of Th1 cells enhances the recruitment potential of the lung leading to recruitment and activation of Th2 cells. This implies that circulating Th2 cells in allergic individuals could enter the lungs in response to infection or inflammation and become activated to trigger allergy.
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PMID:Antigen-nonspecific recruitment of Th2 cells to the lung as a mechanism for viral infection-induced allergic asthma. 1242 21


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