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Results for “Immune Escape”

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At least 127 records · Page 7Linked to original sources
PubMed1992

Herpesviruses--immune escape artists?

Viral persistence depends on the successful avoidance of the host's immunologic surveillance system. This review, which focuses specifically on the herpesviruses, delineates several possible strategies for evading or delaying the immune response. One strategy common to all herpesviruses is the establishment of latency, a state in which the virus may be partially or even completely hidden from the immune system. Other proposed mechanisms of immune evasion include interaction of the virus with components of the humoral immune system, virus-induced modulation of cell-surface recognition structures, and virally mediated interference in antigen processing. Additional strategies include molecular mimicry and the ability of one particular herpesvirus to encode an immunosuppressive cytokine. Although a detailed understanding of the molecular mechanisms of herpesvirus-mediated immune evasion is currently lacking, future studies should identify those critical interactions between host and virus that may prove amenable to therapeutic intervention.

Animals↗
PubMed2005

Human immunodeficiency virus type 1 Vpr impairs dendritic cell maturation and T-cell activation: implications for viral immune escape.

Antigen presentation and T-cell activation are dynamic processes involving signaling molecules present in both APCs and T cells. Effective APC function and T-cell activation can be compromised by viral immune evasion strategies, including those of human immunodeficiency virus type 1 (HIV-1). In this study, we determined the effects of HIV-1 Vpr on one of the initial target of the virus, dendritic cells (DC), by investigating DC maturation, cytokine profiling, and CD8-specific T-cell stimulation function followed by a second signal. Vpr impaired the expression of CD80, CD83, and CD86 at the transcriptional level without altering normal cellular transcription. Cytokine profiling indicated that the presence of Vpr inhibited production of interleukin 12 (IL-12) and upregulated IL-10, whereas IL-6 and IL-1beta were unaltered. Furthermore, DC infected with HIV-1 vpr+ significantly reduced the activation of antigen-specific memory and recall cytotoxic-T-lymphocyte responses. Taken together, these results indicate that HIV-1 Vpr may in part be responsible for HIV-1 immune evasion by inhibiting the maturation of costimulatory molecules and cytokines essential for immune activation.

Antigens, CD↗
PubMed2006

Immune escape of equine herpesvirus 1 and other herpesviruses of veterinary importance.

Equine herpesvirus (EHV)-1 is a pathogen of horses, well known for its ability to induce abortion and nervous system disorders. Clinical signs may occur despite the presence of a virus-specific immune response in the horse. The current review will summarize the research, on how, EHV-1-infected cells can hide from recognition by the immune system. Research findings on immune evasion of EHV-1 will be compared with those of other herpesviruses of veterinary importance.

Animals↗
PubMed1997

Role of Fas ligand (CD95L) in immune escape: the tumor cell strikes back.

Several different tumor types have recently been shown to express functional Fas ligand (FasL), which may represent an additional mechanism of tumor escape. However, the in vivo significance of these findings in the context of potent adversaries such as activated CTL or NK cells remains to be fully established. The potential interactions between tumor cells and the host immune response are thus more complex than previously thought; their elucidation will benefit the rational design of cancer immunotherapy strategies.

Apoptosis↗
PubMed2005

Emergence of immune escape variant of mammary tumors that has distinct proteomic profile and a reduced ability to induce "danger signals".

Breast tumors are shaped, in part, by a process termed immunoediting which selects for immunologically evasive phenotypes. In the present study we used the rat neu-transgenic mouse model of breast cancer and its congenic non-transgenic parental strain, FVB, to explore the phenotype of tumors that emerge in the presence of an immune response directed against the neu antigen. When inoculated into parental FVB mice, a neu-overexpressing mouse mammary carcinoma (MMC) cell line isolated from spontaneous breast tumors of the FVB neu (FVBN202) transgenic mouse, elicited a neu-specific immune response resulting in a tumor rejection because of the presence of the rat neu antigen. However, a neu negative variant (ANV) of MMC arose after a long latency in spite of the neu-specific immune response. We show that compared to MMC, ANV tumor cells have a significantly reduced ability to secrete pro-inflammatory cytokines and the CCL5 chemokine, to express immunostimulatory chaperones, and they have a distinct expression of proteins involved in cell motility, and metabolic and signal transduction pathways. These studies suggest that tumor escape through immunoediting can not be explained by the loss of a single tumor antigen, but rather by a selection process of a tumor variant that has a reduced ability to induce "danger signals" together with up-regulation of proteins involved in the tumor survival. Based on these findings, we propose to target novel antigens over-expressed in the escape variant of breast tumors to treat primary tumor and to prevent tumor relapse.

Animals↗
PubMedDate not supplied

Lost in translation: implications of HIV-1 codon usage for immune escape and drug resistance.

Synonymous nucleotide substitutions in protein-coding sequences are often regarded as evolutionarily neutral and not subject to selective pressure. However, synonymous codons can sometimes lead to different patterns of amino acid substitution by single nucleotide changes. Based on the deconstruction of the standard genetic code, we propose the term 'quasi-synonymous' to describe codons that specify the same amino acid, but lie on different mutational pathways, and we show that in at least one rapidly evolving organism, HIV-1, quasi-synonymy plays a role in its evolution. We present concrete examples that demonstrate the relevance of codon usage in the development of antiretroviral-drug resistance. In the case of the host immune response, the data indicates that viral evasion is achieved through use of codons that lie on the direct path to escape mutants, and equally, permit rapid reversion to wild-type in the absence of these selective pressures. Quasi-synonymy conditions HIV-1 and, potentially, other rapidly evolving organisms in their exploration of the mutational space.

Anti-HIV Agents↗
PubMed1995

Immune escape and tropism of HIV.

HIV-1 cell tropisms are partly determined by the hypervariable loops V1/V2 and V3 in gp120, which also contain epitopes for neutralizing antibodies. Mutations conferring tropism changes can result in escape from neutralization and vice versa. We examine whether variant viruses that can colonize new cell types and simultaneously escape neutralizing antibodies have an enhanced advantage in vivo.

Amino Acid Sequence↗
PubMed2005

Parasite immune escape: new views into host-parasite interactions.

For parasites of humans and animals that rely on vectors or on sexual contact for transmission, it is particularly important that infection does not to terminate before the occurrence of the crucial event that completes its lifecycle (e.g. another mosquito bite). For chronic infection to occur, it is essential that the parasite avoids clearance by the host immune system. Much progress has been made in elucidating the immunological interactions and the molecular mechanisms involved in the process of immune evasion. Mathematical models have also been invaluable in understanding these processes, particularly in the generation of new ideas about a complex form of immune evasion known as antigenic variation whereby a major target of the host immune response is varied during the course of a single infection to avoid recognition.

Animals↗
PubMed2001

Human pancreatic cancer cells express non-functional Fas receptors and counterattack lymphocytes by expressing Fas ligand; a potential mechanism for immune escape.

The aim of this study was to investigate the expression and functional status of Fas ligand (FasL) and its receptor (Fas) in human pancreatic cancers. Using RT-PCR and Western blotting, Fas and FasL were expressed in seven surgically resected pancreatic cancer specimens and five cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. In the resected specimens, pancreatic cancer cells induced apoptosis in the surrounding lymphoid cells. In coculture experiments of pancreatic cancer and Jurkat T cells, 50% of Jurkat T cells underwent apoptosis after 2 days, however, almost all pancreatic cancer cells remained viable. In addition, by testing Fas function using anti-Fas antibody (CH11), all cell lines were resistant to Fas-mediated apoptosis except Capan-1 cells which showed sensitivity similar to that of Jurkat T cells. These results suggest that pancreatic cancer cells evade immune surveillance by expression of FasL and non-functioning Fas that allow them to activated T-cells. These tumor escape mechanisms may contribute to the rapid fatal course of pancreatic cancer.

Apoptosis↗
PubMed1995

Change in tropism upon immune escape by human immunodeficiency virus.

The V3 loop of human immunodeficiency virus type 1 is both a determinant of viral cell tropism and a target for neutralizing antibodies. This relationship was investigated. Selection of a dual-tropic (T cells and macrophages) virus to replicate in CD4+ brain cells results in loss of macrophage tropism and of neutralization by an anti-V3 loop monoclonal antibody. Moreover, selection of the brain-selected variant to escape from V3 loop-specific neutralizing monoclonal antibodies results in the reduction or loss of brain cell tropism and the reacquisition of macrophage tropism. These data may indicate that the antigenic diversification of human immunodeficiency virus type 1 apparent after seroconversion can be selected either by immune responses or by colonization of new cell types.

Amino Acid Sequence↗
PubMed2006

[Anthrax revisited: Bacillus anthracis toxins as novel actors of immune escape?].

The recent bioterrorist attacks have stressed the need of a better knowledge of Bacillus anthracis infection pathophysiology. We present here the increasing interests of B. anthracis studies in term of bio-defense, the main pathogen characteristics, the main clinical features of inhalational anthrax (the pulmonary form of the disease), and recent aspects of its physiopathology. Next, we address the main results concerning the toxin effects on immune system through impairing the dendritic cell functions, and we analyze the singular role of anthrax toxins in immune evasion.

Animals↗
PubMed1996

Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape.

Malignant melanoma accounts for most of the increasing mortality from skin cancer. Melanoma cells were found to express Fas (also called Apo-1 or CD95) ligand (FasL). In metastatic lesions, Fas-expressing T cell infiltrates were proximal to FasL+ tumor cells. In vitro, apoptosis of Fas-sensitive target cells occurred upon incubation with melanoma tumor cells; and in vivo, injection of FasL+ mouse melanoma cells in mice led to rapid tumor formation. In contrast, tumorigenesis was delayed in Fas-deficient lpr mutant mice in which immune effector cells cannot be killed by FasL. Thus, FasL may contribute to the immune privilege of tumors.

Animals↗
PubMed2002

Epigenetic changes in tumor Fas levels determine immune escape and response to therapy.

Epigenetic regulation of gene expression significantly influences cell growth and differentiation. Here we show that epigenetic silencing of Fas determines tumor growth in vivo and apoptotic sensitivity in vitro. In established tumors with epigenetically repressed Fas, restoration of Fas activity either by transfection of fas or treatment with Trichostatin A (TSA), an inhibitor of histone deacetylase, suppresses tumor growth and restores chemosensitivity. The TSA-dependent chemosensitivity and tumor growth control require both tumor Fas and the host NK (natural killer) cell functions. This work demonstrates the importance of epigenetic modification of Fas in tumor progression and immune evasion, and emphasizes the essential interplay between Fas and innate immunity in the control of chemoresistant tumors.

Animals↗
PubMed2005

HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro: implications for immune escape in vivo.

The nonclassical MHC class I molecule HLA-E is the only known ligand for CD94/NKG2A and CD94/NKG2C expressed on NK and CD8+ alphabeta and gammadelta T cells. HLA-E may transmit either activating signals via CD94/NKG2C or inhibitory signals mediated by CD94/NKG2A. Here we show that HLA-E is expressed at mRNA and protein level in human long-term glioma cell lines, primary ex vivo polyclonal glioblastoma cell cultures and surgical glioblastoma specimens. Furthermore, immunohistochemistry revealed an enhanced in vivo expression of HLA-E in gliomas of lower grades and a massive overexpression in grade IV glioblastomas compared with normal CNS tissue. An immune-inhibitory effect of HLA-E on tumor-specific CTL has already been described. We show that siRNA-mediated silencing of HLA-E or blocking of CD94/NKG2A enables NKG2D-mediated lysis of 51Cr-labeled tumor cells by NK cells. Thus, our study provides the first evidence that expression and interaction of HLA-E on cancer cells with CD94/NKG2A expressed on lymphocytes compromises innate anti-tumor immune responses.

Antigens, CD↗
PubMed2005

Relation between viral fitness and immune escape within the hepatitis C virus protease.

BACKGROUND: The hepatitis C virus (HCV) mutates within human leucocyte antigen (HLA) class I restricted immunodominant epitopes of the non-structural (NS) 3/4A protease to escape cytotoxic T lymphocyte (CTL) recognition and promote viral persistence. However, variability is not unlimited, and sometimes almost absent, and factors that restrict viral variability have not been defined experimentally. AIMS: We wished to explore whether the variability of the immunodominant CTL epitope at residues 1073-1081 of the NS3 protease was limited by viral fitness. PATIENTS: Venous blood was obtained from six patients (four HLA-A2+) with chronic HCV infection and from one HLA-A2+ patient with acute HCV infection. METHODS: NS3/4A genes were amplified from serum, cloned in a eukaryotic expression plasmid, sequenced, and expressed. CTL recognition of naturally occurring and artificially introduced escape mutations in HLA-A2-restricted NS3 epitopes were determined using CTLs from human blood and genetically immunised HLA-A2-transgenic mice. HCV replicons were used to test the effect of escape mutations on HCV protease activity and RNA replication. RESULTS: Sequence analysis of NS3/4A confirmed low genetic variability. The major viral species had functional proteases with 1073-1081 epitopes that were generally recognised by cross reactive human and murine HLA-A2 restricted CTLs. Introduction of mutations at five positions of the 1073-1081 epitope prevented CTL recognition but three of these reduced protease activity and RNA replication. CONCLUSIONS: Viral fitness can indeed limit the variability of HCV within immunological epitopes. This helps to explain why certain immunological escape variants never appear as a major viral species in infected humans.

Acute Disease↗
PubMed2005

Vascular endothelial cells have impaired capacity to present immunodominant, antigenic peptides: a mechanism of cell type-specific immune escape.

Vascular endothelial cells (EC) are an exposed target tissue in the course of CTL-mediated alloimmune diseases such as graft-vs-host disease (GVHD) or solid organ transplant rejection. The outcome of an interaction between CTL and target cells is determined by the amount of Ag presented and the costimulatory signals delivered by the target cells. We compared human EC with leukocytes and epithelial cells as targets for peptide-specific, MHC class I-restricted CTL clones. EC were poor targets for immunodominant CTL. Both endogenously processed antigenic proteins and exogenously added antigenic peptides are presented at 50- to 5000-fold lower levels on EC compared with any other target cell analyzed. This quantitative difference fully explained the poor CTL-mediated killing of EC. There was no evidence that lack of costimulation would contribute significantly to this cell type-specific difference in CTL activation. An HLA-A2-specific CTL clone that killed a broad selection of HLA A2-positive target cells equally well, killed EC less efficiently. Our data suggest that EC present a different Ag repertoire compared with other cell types. By this mechanism, these cells may escape an attack by effector CTL, which have been educated by professional APCs and are specific for immunodominant antigenic peptides.

Antigen Presentation↗
PubMed2001

Immune escape of melanoma: first evidence of structural alterations in two distinct components of the MHC class I antigen processing pathway.

Sequence analyses of the transporter associated with antigen processing (TAP) in tumor cell lines with deficient MHC class I surface expression identified a bp deletion at position 1489 near the ATP-binding domain of Tap1, causing a frameshift in one melanoma cell line. The impaired TAP1 protein expression was associated with deficient TAP2 protein expression, peptide binding, translocation, and MHC class I surface expression. Stable TAP1 gene transfer reconstitutes the described defects, whereas lysis by HLA-A2-restricted CTLs was still abrogated. This was attributable to a 2-bp insertion at position 890 in the HLA-A2 gene and was corrected after HLA-A2 cotransfection. This study describes for the first time mutations in two distinct components of the MHC class I antigen processing pathway, suggesting an immune selection against CTLs recognizing both TAP-dependent and -independent T-cell epitopes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗