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1.
2.
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
3.
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
4.
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
5.
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
6.
We are developing vaccines that activate tumor-specific CD4+ T cells. The cell-based vaccines consist of MHC class I+ tumor cells that are genetically modified to express syngeneic MHC class II and costimulatory molecules. Previous studies demonstrated that treatment of mice with established tumors with these vaccines resulted in regression of solid tumors, reduction of metastatic disease, and increased survival time. Optimal vaccines will prime naïve T cells and activate T cells to tumor peptides derived from diverse subcellular compartments, since potential tumor antigens may reside in unique cellular locales. To determine if the MHC class II / costimulatory molecule vaccines fulfill these conditions, the vaccines have been tested for their ability to activate antigen-specific, naïve, transgenic CD4+ T lymphocytes. MHC class II+CD80+ vaccine cells were transfected with hen eggwhite lysozyme targeted to the cytosol, nuclei, mitochondria, or endoplasmic reticulum, and used as antigen-presenting cells to activate I-Ak–restricted, lysozyme-specific CD4+ 3A9 transgenic T cells. Regardless of the cellular location of lysozyme, the vaccines stimulated release of high levels of IFN- and IL-2. If the vaccines coexpressed the MHC class II accessory molecule invariant chain, then IFN- and IL-2 release was significantly reduced. These studies demonstrate that in the absence of invariant chain the MHC class II and CD80 tumor cell vaccines (1) function as antigen-presenting cells to activate naïve, tumor-specific CD4+ cells to endogenously synthesized tumor antigens; (2) polarize the activated CD4+ T cells toward a type 1 response; and (3) present epitopes derived from varied subcellular locales.Abbreviations APC
antigen-presenting cells
- CIITA
MHC class II transactivator
- CytoHEL
HEL targeted to cytoplasm
- ER
endoplasmic reticulum
- ErHEL
HEL targeted to ER
- HEL
hen eggwhite lysozyme
- 3A9
HEL46–61–specific, I-Ak–restricted TCR
- Hph
hygromycin
- Ii
invariant chain
- MAb
monoclonal antibody
- MitoHEL
HEL targeted to mitochondria
- NucHEL
HEL targeted to nucleus
- Puro
puromycin
- TG
transgenic
- Zeo
Zeocin 相似文献
7.
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
8.
Kelchtermans H De Klerck B Mitera T Van Balen M Bullens D Billiau A Leclercq G Matthys P 《Arthritis research & therapy》2005,7(2):R402-R415
Mice with a deficiency in IFN-γ or IFN-γ receptor (IFN-γR) are more susceptible to collagen-induced arthritis (CIA), an experimental
autoimmune disease that relies on the use of complete Freund's adjuvant (CFA). Here we report that the heightened susceptibility
of IFN-γR knock-out (KO) mice is associated with a functional impairment of CD4+CD25+ Treg cells. Treatment of wild-type mice with depleting anti-CD25 antibody after CFA-assisted immunisation with collagen type II
(CII) significantly accelerated the onset of arthritis and increased the severity of CIA. This is an indication of a role
of Treg cells in the effector phase of CIA. IFN-γR deficiency did not affect the number of CD4+CD25+ T cells in the central and peripheral lymphoid tissues. In addition, CD4+CD25+ T cells isolated from naive IFN-γR KO mice had a normal potential to suppress T cell proliferation in vitro. However, after immunisation with CII in CFA, the suppressive activity of CD4+CD25+ T cells became significantly more impaired in IFN-γR-deficient mice. Moreover, expression of the mRNA for Foxp3, a highly
specific marker for Treg cells, was lower. We further demonstrated that the effect of endogenous IFN-γ, which accounts for more suppressive activity
in wild-type mice, concerns both Treg cells and accessory cells. Our results demonstrate that the decrease in Treg cell activity in CIA is counter-regulated by endogenous IFN-γ. 相似文献
9.
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
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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
12.
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
13.
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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The intracellular signal cascades involved in chemokine-stimulated migration of in vitro activated human peripheral blood CD4+ T-lymphocytes were investigated. IP-10-mediated chemotactic response of lymphocytes was decreased in the presence of selective inhibitors of Src-kinases (by 40-45%), PI3-kinases (35-40%), and MAP-kinases ERK1/2 (35-40%) and p38 (20%). Combined addition of specific inhibitors of Src-kinases and PI3-kinases and inhibitors of Src-kinases and ERK1/2 MAP-kinases did not result in the further increase of the inhibitory effect, while the combined addition of specific inhibitors of PI3-kinases and ERK1/2 MAP-kinases decreased migration of CD4+ T-lymphocytes more effectively (by 55-60%) than any individual inhibitor. Immunoblotting analysis of activation of MAP-kinases ERK1/2 and p38 revealed increased level of phosphorylation of ERK1/2 and p38 MAP-kinases in the presence IP-10. Selective inhibitors of Src-kinases and PI3-kinases significantly inhibited phosphorylation of p38 but did not influence phosphorylation of ERK1/2 MAP-kinases. Our results suggest that Src-kinases, PI3-kinases, and ERK1/2 MAP-kinases are involved in intracellular signal cascade activated during IP-10-stimulated migration of T-lymphocytes, whereas p38 MAP-kinases do not participate in the migration process, although its activation induced by IP-10 depends on Src-kinases and PI3-kinases. 相似文献
17.
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18.
19.
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
20.
Tamaki T Okada Y Uchiyama Y Tono K Masuda M Wada M Hoshi A Akatsuka A 《Histochemistry and cell biology》2007,128(4):349-360
In order to establish the practical isolation and usage of skeletal muscle-derived stem cells (MDSCs), we determined reconstitution
capacity of CD34−/CD45− (Sk-DN) cells as a candidate somatic stem cell source for transplantation. Sk-DN cells were enzymatically isolated from GFP
transgenic mice (C57/BL6N) skeletal muscle and sorted using fluorescence activated cell sorting (FACS), and expanded by collagen
gel-based cell culture with bFGF and EGF. The number of Sk-DN cells was small after sorting (2–8 × 104); however, the number increased 10–20 fold (2–16 × 105) after 6 days of expansion culture, and the cells maintained immature state and multipotency, expressing mRNAs for mesodermal
and ectodermal cell lineages. Transplantation of expanded Sk-DN cells into the severe muscle damage model (C57/BL6N wild-type)
resulted in the synchronized reconstitution of blood vessels, peripheral nerves and muscle fibers following significant recovery
of total muscle mass (57%) and contractile function (55%), whereas the non-cell-transplanted control group showed around 20%
recovery in both factors. These reconstitution capacities were supported by the intrinsic plasticity of Sk-DN cells that can
differentiate into muscular (skeletal muscle), vascular (pericyte, endothelial cell and smooth muscle) and peripheral nerve
(Schwann cells and perineurium) cell lineages that was revealed by transplantation to non-muscle tissue (beneath renal capsule)
and fluorescence in situ hybridization (FISH) analysis. 相似文献