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1.
Brown IE Mashayekhi M Markiewicz M Alegre ML Gajewski TF 《Apoptosis : an international journal on programmed cell death》2005,10(1):5-11
Maintenance of a sufficient population of naïve CD8+ T cells in the peripheral lymphoid compartment is critical for immunocompetence. Peripheral T cell number is a function of T cell generation, survival, and death. Homeostasis, a critical balance between survival and death, must exist to prevent either lymphopenia or lymphocytosis. In the current review, we discuss known requirements for the survival of naïve peripheral CD8+ T cells as well as mechanisms of death when survival signals are lost. We also discuss associations between survival and homeostasis-driven proliferation, and highlight the gaps in our knowledge of these critical processes. 相似文献
2.
Zloza A Jagoda MC Lyons GE Graves MC Kohlhapp FJ O'Sullivan JA Lacek AT Nishimura MI Guevara-Patiño JA 《Cancer immunology, immunotherapy : CII》2011,60(2):291-297
CD8+ T cell function depends on a finely orchestrated balance of activation/suppression signals. While the stimulatory role of
the CD8 co-receptor and pleiotropic capabilities of TGF-β have been studied individually, the influence of CD8 co-receptor
on TGF-β function in CD8+ T cells is unknown. Here, we show that while CD8 enhances T cell activation, it also enhances susceptibility to TGF-β-mediated
immune suppression. Using Jurkat cells expressing a full-length, truncated or no αβCD8 molecule, we demonstrate that cells
expressing full-length αβCD8 were highly susceptible, αβCD8-truncated cells were partially susceptible, and CD8-deficient
cells were completely resistant to suppression by TGF-β. Additionally, we determined that inhibition of Lck rendered mouse
CD8+ T cells highly resistant to TGF-β suppression. Resistance was not associated with TGF-β receptor expression but did correlate
with decreased Smad3 and increased Smad7 levels. These findings highlight a previously unrecognized third role for CD8 co-receptor
which appears to prepare activated CD8+ T cells for response to TGF-β. Based on the important role which TGF-β-mediated suppression plays in tumor immunology, these
findings unveil necessary considerations in formulation of CD8+ T cell-related cancer immunotherapy strategies. 相似文献
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Based on the difference in the CD14 and CD16 expression, two subsets of monocytes were identified in human and other mammalian
blood. These subsets have different patterns of adhesion molecules and chemokine receptors that suggests the different mode
of their interaction with endothelium and tissue traffic. Here, we investigated the ability of CD14+CD16+ and CD14++CD16− monocytes to adhere to endothelial cell monolayer in presence or absence of pro- and anti-inflammatory cytokines. We demonstrated
that CD14+CD16+ monocytes had a higher level of adhesion to intact monolayer of endothelial cells than CD14++CD16− monocytes. Adhesion of CD14++CD16− and CD14+CD16+ monocytes significantly increased in the presence of TNFα or its combination with other cytokines. IFNγ and IL-4 alone did
not affect the adhesion of monocytes. These results show that CD14++CD16− and CD14+CD16+ monocytes can be recruited to the inflamed endothelium, but CD14+CD16+ monocytes adhere to endothelial cells without inflammations twice as strongly as CD14++CD16− monocytes. 相似文献
5.
Acute coronary syndrome (ACS) is a group of clinical symptoms that results from complete or partial occlusive thrombus, which
is caused by coronary an atherosclerotic plaque rupture or erosion. According to a recent study, CD4+ CD28− T cells are found in atherosclerotic plaques and the peripheral circulation blood in patients with ACS, these cells play
an important role in plaque ruptures. CD4+ CD28− T cells are an unusual subset of helper cells, which expand and have harmful effects in ACS. In this review, we discuss the
current issues on the generation of CD4+ CD28− T cells and focus on their phenotypic and functional characteristics relevant to the development of cardiovascular events.
Targeting the CD4+ CD28− T cells subset in ACS could provide novel therapeutic means to prevent acute life-threatening coronary events. 相似文献
6.
Voelkl S Moore TV Rehli M Nishimura MI Mackensen A Fischer K 《Cancer immunology, immunotherapy : CII》2009,58(5):709-718
The immune attack against malignant tumors require the concerted action of CD8+ cytotoxic T lymphocytes (CTL) as well as CD4+ T helper cells. The contribution of T cell receptor (TCR) αβ+ CD4− CD8− double-negative (DN) T cells to anti-tumor immune responses is widely unknown. In previous studies, we have demonstrated
that DN T cells with a broad TCR repertoire are present in humans in the peripheral blood and the lymph nodes of healthy individuals.
Here, we characterize a human DN T cell clone (T4H2) recognizing an HLA-A2-restricted melanoma-associated antigenic gp100-peptide
isolated from the peripheral blood of a melanoma patient. Antigen recognition by the T4H2 DN clone resulted in specific secretion
of IFN-γ and TNF. Although lacking the CD8 molecule the gp100-specifc DN T cell clone was able to confer antigen-specific
cytotoxicity against gp100-loaded target cells as well as HLA-A2+ gp100 expressing melanoma cells. The cytotoxic capacity was found to be perforin/granzymeB-dependent. Together, these data
indicate that functionally active antigen-specific DN T cells recognizing MHC class I-restricted tumor-associated antigen
(TAA) may contribute to anti-tumor immunity in vivo.
A. Mackensen and K. Fischer contributed equally to this work and should be considered joint senior authors. This work was
supported by the Deutsche Forschungsgemeinschaft (MA 1351/5-1, KFO 146) and NIH grants CA90873, CA102280, 104947 (MIN).
Companion paper: “Relationship between CD8-dependent antigen recognition, T cell functional avidity, and tumor cell recognition”
by Tamson V. Moore et al. doi: . 相似文献
7.
Godefroy E Wang Y Souleimanian NE Scotto L Stevanovic S Chen YT Valmori D Ayyoub M 《Cancer immunology, immunotherapy : CII》2007,56(8):1183-1192
Proteins encoded by genes of the SSX family are specifically expressed in tumors and are therefore relevant targets for cancer immunotherapy. One of the first identified family members, SSX-1, is expressed in a large fraction of synovial sarcomas as a fusion protein together with the product of the SYT gene. In addition, the full-length SSX-1 antigen is frequently expressed in tumors of several other histological types such as sarcoma, melanoma, hepatocellular carcinoma, ovarian cancer and myeloma. To date, however, SSX-1 specific T cell responses have not been investigated and no SSX-1 derived T cell epitopes have been described. Here, we have assessed the presence of CD4(+) T cells directed against the SSX-1 antigen in circulating lymphocytes of cancer-free individuals. After a single in vitro stimulation with a pool of peptides spanning the entire SSX-1 protein we could detect and isolate SSX-1-specific CD4(+) T cells from 5/5 donors analyzed. SSX-1-specific polyclonal populations isolated from these cultures recognized peptides located in three distinct regions of the protein containing clusters of sequences with significant predicted binding to frequently expressed MHC class II alleles. Characterization of specific clonal CD4(+) T cell populations derived from one donor allowed the identification of several naturally processed epitopes recognized in association with HLA-DR. These data document the existence of a significant repertoire of CD4(+) T cells specific for SSX-1 derived sequences in circulating lymphocytes of any individual that can be exploited for the development of both passive and active immunotherapeutic approaches to control disease evolution in cancer patients. 相似文献
8.
NKT cells, na?ve CD4(+) T cells, and TCR-gammadelta T cells belong to distinct T cell lineages but all express T cell receptors generated through random combinatorial joining of V-(D)-J genes. These distinct lineage T cells also possess the property of promptly activating the IL-4 gene upon T cell receptor stimulation. A comparative accounting of features as they pertain to IL-4 inducibility in these three distinct lineage T cells is provided here. 相似文献
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The majority of cells infected with the human immunodeficiency virus are activated CD4+ T cells, which can be treated with antiretoviral drugs. However, an obstacle to eradication is the presence of viral reservoirs, such as latently infected CD4+ T cells. Such cells may be less susceptible to antiretroviral drugs and may persist at low levels during treatment. We introduce a model of impulsive differential equations that describe T cell and drug interactions. We make the extreme assumption that latently infected cells are unaffected by drugs, in order to answer the research question: Can the viral reservoir of latently infected cells be eradicated using current antiretroviral therapy? We analyse the model in both the presence and absence of drugs, showing that, if the frequency of drug taking is sufficiently high, then the number of uninfected CD4+ T cells approaches the number of T cells in the uninfected immune system. In particular, this implies that the latent reservoir will be eliminated. It follows that, with sufficient application of drugs, latently infected cells cannot sustain a viral reservoir on their own. We illustrate the results with numerical simulations. 相似文献
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Jennifer M Kress-Bennett Garth D Ehrlich Ashley Bruno J Christopher Post Fen Z Hu Thomas F Scott 《BMC neurology》2011,11(1):155
Background
There are a lack of biomarkers which can be used to predict clinical outcomes for multiple sclerosis (MS) patients receiving interferon beta (IFN-β). Thus the objective of this study was to characterize changes in CD4+ T-lymphocyte expression in an unbiased manner following initiation of intramuscular (IM) IFN-β-1a treatment, and then to verify those findings using marker-specific assays. 相似文献14.
Bone marrow-derived cells have been postulated as a source of multipotent mesenchymal stem cells (MSC). However, the whole
fraction of MSC remains heterogeneous and the expansion of primitive subset of these cells is still not well established.
Here, we optimized the protocol for propagating the low-adherent subfraction of MSC which results in long-term expansion of
population characterized by CD45−CD14+CD34+ phenotype along with expression of common MSC markers. We established that the expanded MSC are capable of differentiating
into endothelial cells highly expressing angiogenic markers and exhibiting functional properties of endothelium. Moreover,
we found these cells to be multipotent and capable of giving rise into cells from neuronal lineages. Interestingly, the expanded
MSC form characteristic cellular spheres in vitro indicating primitive features of these cells. In sum, we isolated the novel multipotent subpopulation of CD45−CD14+ CD34+ bone marrow-derived cells that could be maintained in long-term culture without losing this potential. 相似文献
15.
Murakami D Suzuki MF da Silva Dias M Okazaki K 《Radiation and environmental biophysics》2004,43(2):91-99
Among various types of ionizing radiation, the beta emitter radionuclides are involved in many sectors of human activity, such as nuclear medicine, nuclear industries and biomedicine, with a consequently increased risk of accidental, occupational or therapeutic exposure. Despite their recognized importance, there is little information about the effect of beta particles at the cellular level when compared to other types of ionizing radiation. Thus, the objective of the present study was to evaluate the genotoxic and cytotoxic effects of 90Sr/90Y—a pure, highly energetic beta source—on Chinese hamster ovary (CHO) cells and to compare them with data obtained with 60Co. CHO cells irradiated with different doses of 60Co (0.34 Gy min–1) and 90Sr/90Y (0.23 Gy min–1) were processed for analysis of clonogenic death, induction of micronuclei (MN) and interphase death. The survival curves obtained for both types of radiation were fitted by the exponential quadratic model and were found to be similar. Also, the cytogenetic results showed similar frequencies of radio-induced MN between gamma and beta radiations and the MN distribution pattern among cells did not follow the expected Poisson probability pattern. The relative variance values were significantly higher in cells irradiated with 90Sr/90Y than with 60Co in all exposure doses. The irradiated cells showed more necrotic cells 72 h and 96 h after exposure to beta than to gamma radiation. In general, the 90Sr/90Y -radiation was more damaging than 60Co -rays. The data obtained also demonstrated the need to use several parameters for a better estimate of cellular sensitivity to the action of genotoxic agents, which would be important in terms of radiobiology, oncology and therapeutics. 相似文献
16.
Interplay between the host and influenza virus has a pivotal role for the outcome of infection. The matrix proteins M2/BM2
from influenza (A and B) viruses are small type III integral membrane proteins with a single transmembrane domain, a short
amino-terminal ectodomain and a long carboxy-terminal cytoplasmic domain. They function as proton channels, mainly forming
a membrane-spanning pore through the transmembrane domain tetramer, and are essential for virus assembly and release of the
viral genetic materials in the endosomal fusion process. However, little is known about the host factors which interact with
M2/BM2 proteins and the functions of the long cytoplasmic domain are currently unknown. Starting with yeast two-hybrid screening
and applying a series of experiments we identified that the β1 subunit of the host Na+/K+-ATPase β1 subunit (ATP1B1) interacts with the cytoplasmic domain of both the M2 and BM2 proteins. A stable ATP1B1 knockdown
MDCK cell line was established and we showed that the ATP1B1 knockdown suppressed influenza virus A/WSN/33 replication, implying
that the interaction is crucial for influenza virus replication in the host cell. We propose that influenza virus M2/BM2 cytoplasmic
domain has an important role in the virus-host interplay and facilitates virus replication. 相似文献
17.
Gordana Konjević Katarina Mirjačić Martinović Ana Vuletić Vladimir Jurisić Ivan Spužić 《The Journal of membrane biology》2009,230(3):113-123
The aim of this study was to estimate the distribution and density of a representative set of activating and inhibitory receptors
on gated natural killer (NK) cells, as well as on their bright and dim subsets, and to correlate the receptor expression with
NK cell activity for healthy individuals on CD3−CD16+ NK cells. We show that in 43 healthy controls NK cell activity against K562 target cells was 37.34% (E:T, 80:1) by standard
chromium release assay. The expression of receptors on NK cells and their subsets was analyzed by flow cytometry. The cytotoxic
CD3−CD16bright NK subset constituted 78.97%, while the regulatory CD3−CD16dim NK subset constituted 21.03% of NK cells. We show the distribution of NKG2D, CD161, CD158a, and CD158b receptors on CD3−CD16+ NK cells in peripheral blood lymphocytes (PBLs), on gated NK cells, and on the CD3−CD16bright and CD3−CD16dim subsets. Contrary to CD158a and CD158b killer immunoglobulin-like receptors (KIRs), there is a significant positive correlation
of NKG2D and CD161 expression with NK cytotoxicity. We show the kinetics of change in CD3−CD16+NK/K562 conjugate composition, together with the stronger target binding capacity of CD16bright NK cells. Furthermore, we show that after coculture of PBLs with K562 the expression of CD107a, a degranulation marker, on
CD3−CD16+NK cells and subsets is time dependent and significantly higher on the cytotoxic CD3−CD16bright NK subset. The novel data obtained regarding expression of NK cell activating and inhibitory receptors for healthy individuals
may aid in detecting changes that are associated with various diseases. 相似文献
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The structures and stabilities of eleven N13
+ and N13
– isomers have been investigated with second-order Møller–Plesset (MP2) and density functional theory (DFT) methods. Five N13
+ isomers and six N13
– isomers are all reasonable local minima on their potential energy hypersurfaces. The most stable N13
+ cation is structure C-2 with C2v symmetry, which contains a pentazole ring and two N4 open chains. It is different from those of the N7
+ and N9
+ clusters, but similar to the N11
+ cluster. Meanwhile, the most stable N13
– structure A-2 is composed of a pentazole ring and a six-membered ring connected by two nitrogen atoms. It is not only different from those of the N7
– and N9
– clusters, but also from the N11
– cluster. The decomposition pathways of structures C-2 and A-2 were investigated at the B3LYP/(aug)-cc-pVDZ level. From the barrier heights of the structures C-2 and A-2 decomposition processes, it is suggested that C-2 is difficult to observe experimentally and A-2 may be observed as a short-lived species.
Figure Optimized geometrical parameters of N13
+ isomer C-2
相似文献
20.
V. E. Yurinskaya T. S. Goryachaya A. A. Rubashkin A. V. Shirokova A. A. Vereninov 《Cell and Tissue Biology》2010,4(5):457-463
The K+, Na+, and Cl− balance and K+ (Rb+) and 36Cl− fluxes in U937 cells induced to apoptosis by 0.2 or 1 μM staurosporine were studied using flame emission and radioisotope
techniques. It is found that two-thirds of the total decrease in the amount of intracellular osmolytes in apoptotic cells
is accounted for by monovalent ions and one-third consists of other intracellular osmolytes. A decrease in the amount of monovalent
ions results from a decrease in the amount of K+ and Cl− and an increase in the Na+ content. The rate of 36Cl−, Rb+ (K+), and 22Na+ equilibration between cells and the medium was found to significantly exceed the rate of apoptotic change in the cellular
ion content, which indicates that unidirectional influxes and effluxes during apoptosis may be considered as being in near
balance. The drift of the ion flux balance in apoptosis caused by 0.2 μM staurosporine was found to be associated with the
increased ouabain-resistant Rb+ (K+) channel influx and insignificantly altered the ouabain-sensitive pump influx. Severe apoptosis induced by 1 μM staurosporine
is associated with reduced pump fluxes and slightly changed channel Rb+ (K+) fluxes. In apoptotic cells, the 1.4–1.8-fold decreased Cl− level is accompanied by a 1.2–1.6-fold decreased flux. 相似文献