921 resultados para Lymphocytes CD4 and CD8
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Chlamydia pneumoniae commonly causes respiratory tract infections in children, and epidemiological investigations strongly link infection to the pathogenesis of asthma. The immune system in early life is immature and may not respond appropriately to pathogens. Toll-like receptor (TLR)2 and 4 are regarded as the primary pattern recognition receptors that sense bacteria, however their contribution to innate and adaptive immunity in early life remains poorly defined. We investigated the role of TLR2 and 4 in the induction of immune responses to Chlamydia muridarum respiratory infection, in neonatal wild-type (Wt) or TLR2-deficient (/), 4/ or 2/4/ BALB/c mice. Wt mice had moderate disease and infection. TLR2/ mice had more severe disease and more intense and prolonged infection compared to other groups. TLR4/ mice were asymptomatic. TLR2/4/ mice had severe early disease and persistent infection, which resolved thereafter consistent with the absence of symptoms in TLR4/ mice. Wt mice mounted robust innate and adaptive responses with an influx of natural killer (NK) cells, neutrophils, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, and activated CD4+ and CD8+ T-cells into the lungs. Wt mice also had effective production of interferon (IFN) in the lymph nodes and lung, and proliferation of lymph node T-cells. TLR2/ mice had more intense and persistent innate (particularly neutrophil) and adaptive cell responses and IL-17 expression in the lung, however IFN responses and T-cell proliferation were reduced. TLR2/4/ mice had reduced innate and adaptive responses. Most importantly, neutrophil phagocytosis was impaired in the absence of TLR2. Thus, TLR2 expression, particularly on neutrophils, is required for effective control of Chlamydia respiratory infection in early life. Loss of control of infection leads to enhanced but ineffective TLR4-mediated inflammatory responses that prolong disease symptoms. This indicates that TLR2 agonists may be beneficial in the treatment of early life Chlamydia infections and associated diseases.
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The role of the immune system is to protect an organism against pathogens while maintaining tolerance against self. T cells are an essential component of the immune system and they develop in the thymus. The AIRE (autoimmune regulator) gene product plays an important role in T cell development, as it promotes expression of peripheral tissue antigens in the thymus. Developing T cells, thymocytes, which recognize self-antigens with high affinity are deleted. However, this deletion process is not perfect and not all autoreactive T cells are destroyed. When the distinction between self and non-self fails, tolerance breaks and the immune system attacks the host s own tissues. This results in autoimmunity. Regulatory T cells contribute to the maintenance of self-tolerance. They can actively suppress the function of autoreactive cells. Several populations of cells with regulatory properties have been described, but the best characterized population is the natural regulatory T cells (Treg cells), which develop in the thymus and express the transcription factor FOXP3. The thymic development of Treg cells in humans is the subject of this thesis. Thymocytes at different developmental stages were analyzed using flow cytometry. The CD4-CD8- double-negative (DN) thymocytes are the earliest T cell precursors in the T cell lineage. My results show that the Treg cell marker FOXP3 is up-regulated already in a subset of these DN thymocytes. FOXP3+ cells were also found among the more mature CD4+CD8+ double-positive (DP) cells and among the CD4+ and CD8+ single-positive (SP) thymocytes. The different developmental stages of the FOXP3+ thymocytes were isolated and their gene expression examined by quantitative PCR. T cell receptor (TCR) repertoire analysis was used to compare these different thymocyte populations. My data show that in humans commitment to the Treg cell lineage is an early event and suggest that the development of Treg cells follows a linear developmental pathway, FOXP3+ DN precursors evolving through the DP stage to become mature CD4+ Treg cells. Most T cells have only one kind of TCR on their cell surface, but a small fraction of cells expresses two different TCRs. My results show that the expression of two different TCRs is enriched among Treg cells. Furthermore, both receptors were capable of transmitting signals when bound by a ligand. By extrapolating flow cytometric data, it was estimated that the majority of peripheral blood Treg cells are indeed dual-specific. The high frequency of dual-specific cells among human Treg cells suggests that dual-specificity has a role in directing these cells to the Treg cell lineage. It is known that both genetic predisposition and environmental factors influence the development of autoimmunity. It is also known that the dysfunction or absence of Treg cells leads to the development of autoimmune manifestations. APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) is a rare monogenic autoimmune disease, caused by mutations in the AIRE gene. In the absence of AIRE gene product, deletion of self-specific T cells is presumably disturbed and autoreactive T cells escape to the periphery. I examined whether Treg cells are also affected in APECED. I found that the frequency of FOXP3+ Treg cells and the level of FOXP3 expression were significantly lower in APECED patients than in controls. Additionally, when studied in cell cultures, the suppressive capacity of the patients' Treg cells was impaired. Additionally, repertoire analysis showed that the TCR repertoire of Treg cells was altered. These results suggest that AIRE contributes to the development of Treg cells in humans and the selection of Treg cells is impaired in APECED patients. In conclusion, my thesis elucidates the developmental pathway of Treg cells in humans. The differentiation of Tregs begins early during thymic development and both the cells dual-specificity and AIRE probably affect the final commitment of Treg cells.
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Glycodelin A (GdA) is one of the progesterone inducible endometrial factors that protect the fetal semiallograft from maternal immune rejection. The immumoregulatory effects of GdA are varied, with diverse effects on the fate and function of most immune cell types. Its effects on T cells are particularly relevant as it is capable of regulating T cell activation, differentiation, as well as apoptosis. We have previously reported that GdA triggers mitochondrial stress and apoptosis in activated T cells by a mechanism that is distinct and independent of its effects on T cell activation. In this study we describe the characterization of a cell surface receptor for GdA on T cells. Our results reveal a novel calcium-independent galactose-binding lectin activity of GdA, which is responsible for its apoptogenic function. This discovery adds GdA to a select group of soluble immunoregulatory lectins that operate within the feto-placental compartment, the only other members being the galectin family proteins. We also report for the first time that both CD4(+) and CD8(+) T cell subsets are equally susceptible to inhibition with GdA, mediated by its novel lectin activity. We demonstrate that GdA selectively recognizes complex-type N-linked glycans on T cell surface glycoproteins. and propose that the galectin-1 glycoprotein receptor CD7 maybe a novel target for GdA on T cells. This study, for the first time, links the lectin activity of GdA to its biological function.
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Mycobacterium indicus pranii (MIP) is approved for use as an adjuvant (Immuvac/Cadi-05) in the treatment of leprosy. In addition, its efficacy is being investigated in clinical trials on patients with tuberculosis and different tumors. To evaluate and delineate the mechanisms by which autoclaved MIP enhances anti-tumor responses, the growth of solid tumors consisting of Sp2/0 (myeloma) and EL4 (thymoma) cells was studied in BALB/c and C57BL/6 mice, respectively. Treatment of mice with a single intra-dermal (i.d.) injection of MIP 3 days after Sp2/0 implantation greatly suppresses tumor growth. MIP treatment of tumor bearing mice lowers Interleukin (IL)6 but increases IL12p70 and IFN? amounts in sera. Also, increase in CD8+ T cell mediated lysis of specific tumor targets and production of high amounts of IL2 and IFN? by CD4+ T cells upon stimulation with specific tumor antigens in MIP treated mice is observed. Furthermore, MIP is also effective in reducing the growth of EL4 tumors; however, this efficacy is reduced in Ifn?-/- mice. In fact, several MIP mediated anti-tumor responses are greatly abrogated in Ifn?-/- mice: increase in serum Interleukin (IL)12p70 amounts, induction of IL2 and lysis of EL4 targets by splenocytes upon stimulation with specific tumor antigens. Interestingly, tumor-induced increase in serum IL12p70 and IFN? and reduction in growth of Sp2/0 and EL4 tumors by MIP are not observed in nonobese diabetic severe combined immunodeficiency mice. Overall, our study clearly demonstrates the importance of a functional immune network, in particular endogenous CD4+ and CD8+ T cells and IFN?, in mediating the anti-tumor responses by MIP.
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To better understand vaccine-induced protection and its potential failure in light of recent whooping cough resurgence, we evaluated quantity as well as quality of memory T cell responses in B. pertussis-vaccinated preadolescent children. Using a technique based on flow cytometry to detect proliferation, cytokine production and phenotype of antigen-specific cells, we evaluated residual T cell memory in a cohort of preadolescents who received a whole-cell pertussis (wP; n=11) or an acellular pertussis vaccine (aP; n=13) during infancy, and with a median of 4 years elapsed from the last pertussis booster vaccine, which was aP for all children. We demonstrated that B. pertussis-specific memory T cells are detectable in the majority of preadolescent children several years after vaccination. CD4(+) and CD8(+) T cell proliferation in response to pertussis toxin and/or filamentous hemagglutinin was detected in 79% and 60% of the children respectively, and interferon- or tumor necrosis factor- producing CD4(+) T cells were detected in 65% and 53% of the children respectively. Phenotyping of the responding cells showed that the majority of antigen-specific cells, whether defined by proliferation or cytokine production, were CD45RA(-)CCR7(-) effector memory T cells. Although the time since the last booster vaccine was significantly longer for wP-compared to aP-vaccinated children, their proliferation capacity in response to antigenic stimulation was comparable, and more children had a detectable cytokine response after wP- compared to aP-vaccination. This study supports at the immunological level recent epidemiological studies indicating that infant vaccination with wP induces longer lasting immunity than vaccination with aP-vaccines.
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Inflammation can promote or inhibit cancer progression. In this study we have addressed the role of the proinflammatory cytokine thymic stromal lymphopoietin (TSLP) during skin carcinogenesis. Using conditional loss- and gain-of-function mouse models for Notch and Wnt signaling, respectively, we demonstrate that TSLP-mediated inflammation protects against cutaneous carcinogenesis by acting directly on CD4 and CD8 Tcells. Genetic ablation of TSLP receptor (TSLPR) perturbs T-cell-mediated protection and results in the accumulation of CD11b(+)Gr1(+) myeloid cells. These promote tumor growth by secreting Wnt ligands and augmenting β-catenin signaling in the neighboring epithelium. Epithelial specific ablation of β-catenin prevents both carcinogenesis and the accumulation of CD11b(+)Gr1(+) myeloid cells, suggesting tumor cells initiate a feed-forward loop that induces protumorigenic inflammation.
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La protine Nef du VIH-1 joue un rle important dans la pathogense du VIH-1 en modulant les voies de signalisation de la cellule hte. La signalisation par le TcR est essentielle la slection positive pour gnrer les cellules simples positives (SP) CD4+ et simples positives (SP) CD8+, processus largement dpendant de lactivit de la Src kinase Lck et de son habilet lier la queue cytoplasmique des corcepteurs CD4 et CD8. Nous avons prcdemment trouv que lexpression de Nef dans le VIH ou VIS peut induire une svre dpltion des thymocytes et une baisse dexpression du corcepteur CD4 la membrane. Nous avons galement montr que Nef bloque la gnration des thymocytes doubles positifs (DP) CD4+ CD8+ en plus daltrer la transition des cellules DP vers CD4+ SP. Par contre, ce phnotype est rcuprable par plusieurs approches dont le croisement dune souris transgniques exprimant Nef avec une souris exprimant la forme constitutivement active de Lck Y505F. Les rsultats indiquent que la maturation des cellules CD4+ est altre par le dysfonctionnement de la signalisation CD4-Lck. Toutefois, les mcanismes molculaires par lesquels Nef contribue au bloc de la gnration des cellules CD4+ dans le thymus demeurent trs imprcis. Dans cette tude, en utilisant des approches biochimiques et de microscopie confocale, nous avons trouv que les thymocytes transgniques Nef+ expriment plus de Lck que les thymocytes Nef-. Malgr cette augmentation, une partie significative de Lck est incapable datteindre la membrane plasmique. Cette fraction tait significativement accumule dans un compartiment intracellulaire des thymocytes transgniques exprimant Nef. galement, en utilisant la technique dessai kinase in vitro, nous avons trouv que lactivit kinase de Lck est significativement augmente dans les thymocytes transgniques mais demeure stable suite une stimulation par un -CD3 + -CD4. galement, comparativement aux thymocytes Nef-, la kinase Lck dans les thymocytes transgniques tait rsistante la dgradation suite une stimulation. En examinant le statut de c-Cbl, le principal rgulateur ngatif de Lck, nous avons montr que c-Cbl colocalise faiblement avec Lck, malgr son hyperphosphorylation constitutive. Ceci pourrait expliquer lchec de la dgradation de Lck. En plus, nous avons trouv que suite une stimulation par un -CD3 + -CD4, la phosphorylation de Zap-70 en tyrosine 493 par Lck est diminue, rsultant dune importante baisse de lactivit kinase de Zap-70 et dun bloc des premiers vnements de la voie de signalisation par le TcR. Ces donnes indiquent que la signalisation CD4-Lck est interrompue par la prsence de Nef.
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Les premires cellules prognitrices lympho-mylodes (LMPP) entrent dans le thymus et commencent leur processus de diffrenciation au stade double ngatif (DN, CD4-CD8-). Aprs un rarrangement fonctionnel de la chaine bta de leur rcepteur des cellules T (RCT), les cellules reoivent des signaux de diffrenciation, de prolifration, de survie et de slection et passent au stade double positif (DP, CD4+CD8+). Ensuite, la chaine alpha du RCT est rarrange et teste via les slections positive et ngative. Si le RCT reoit un signal ni trop fort, ni trop faible, les cellules passent au stade simple positif o elles exprimeront soit la molcule CD4 ou CD8. ERK3, une MAPK non-conventionnelle, joue un rle important dans le dveloppement thymique. Des tudes prcdentes ont dmontr quune dficience en ERK3 diminue de 50 % la cellularit thymique et de 75% le nombre de cellules simples positives CD4 (CD4SP). Nous avons pos comme hypothses quil y a une augmentation de lapoptose chez les thymocytes DP de souris Erk3-/- et que cette dficience chez les thymocytes DP affecterait la slection positive des cellules DP, rduisant ainsi le nombre de thymocytes CD4SP. Afin de vrifier la premire hypothse, nous avons regard les niveaux dapoptose grce la cytomtrie en flux et par immunohistochimie. Dans les deux cas, nous tions incapables de dtecter une diffrence du niveau dapoptose chez les thymocytes DP entre les souris Erk3+/+ et Erk3-/-. Ensuite, nous nous sommes poss la question suivante : La demi-vie des thymocytes DP Erk3-/- tait-elle plus courte que le type sauvage? La demi-vie des thymocytes DP a t mesure laide de ltude des rarrangements secondaires de la chaine alpha du RCT par PCR semi-quantitatif et laide de cultures de thymus ftaux. En effet, ERK3 semble important pour prolonger la demi-vie des thymocytes DP. Ensuite, nous avons utilis des marqueurs cellulaires diffrentiels (CD69, CD5 et RCT) pour regarder si les thymocytes DP sont capables de passer la slection positive. En effet, il y a moins de thymocytes DP Erk3-/- qui sont CD69fort, CD5fort et RCTfort. Finalement, nous voulons savoir si les fonctions de ERK3 passent par MK5, son seul partenaire dinteraction connu ce jour. Aprs la caractrisation du thymus de la souris Mk5-/-, nous observons que seulement la rduction du nombre de thymocytes CD4SP est identique celle des thymocytes CD4SP de la souris Erk3-/-. En conclusion, ces rsultats rvlent des fonctions importantes pour la molcule ERK3 lors du processus de slection positive, le maintient de la demi-vie des thymocytes DP et lors de la rgulation de dveloppement thymique de manire MK5-dpendante et -indpendante.
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Le virus de lhpatite C (VHC) infecte ~185 millions dindividus dans le monde. Malgr le dveloppement des nouvelles thrapies diriges contre le VHC, on compte deux millions de nouvelles infections chaque anne, en particulier dans les pays sous-dvelopps et les populations marginalises. Comme pour la plupart des virus infection chronique, le dveloppement dun vaccin prophylactique efficace est limit par le manque de caractrisation des dterminants de la mmoire immunitaire protectrice lors des pisodes de rinfection naturelle chez les tres humains. Le VHC reprsente un modle unique au sein des virus infection chronique pour tudier limmunit protectrice. En effet ~30% des patients infects par le VHC peuvent tre guris suite un premier pisode dinfection spontanment. Dans cette thse, nous avons tudi limmunit protectrice contre le VHC dans une cohorte dutilisateurs de drogues par injection qui sont risque dtre infects ou rinfects. Notre hypothse est que la majorit des patients qui ont rsolu une premire infection par le VHC sont protgs contre le dveloppement dune infection chronique sils sont rexposs. Cette immunit protectrice est associe la prsence des cellules T CD4 et CD8 polyfonctionnelles qui possdent des frquences, magnitudes et avidits leves. La capacit protectrice des cellules T mmoire contre les squences variables du VHC est dpendante de la diversit et flexibilit du rpertoire de leurs rcepteurs de cellules T (TCR), qui reconnaissent les squences variables des pitopes cibls. Notre premier objectif tait de dfinir et dtailler les dterminants de limmunit protectrice confre par les cellules T spcifiques du VHC. Nos rsultats ont montr que la protection pendant lpisode de rinfection tait associe une augmentation de la magnitude et du spectre des rponses spcifiques par les cellules T CD4 et CD8 polyfonctionnelles, ainsi que par lapparition dune population de cellules T ttramre+ CD8+ effectrices qui expriment faiblement le marqueur CD127 (CD127lo) lors du pic de la rponse. Chez les patients qui ont dvelopp une infection chronique pendant lpisode de rinfection, nous avons observ une expansion trs limite des cellules T CD4 et CD8. Le squenage des pitopes cibls par les cellules T CD8 chez ces patients qui sont non-protgs a montr que les squences de ces pitopes sont diffrentes des squences de rfrence qui taient utilises pour tous les essais immunologiques de cette tude. Le deuxime objectif tait danalyser la dynamique du rpertoire des TCRs des cellules T CD8 spcifiques chez les patients protgs versus les patients non-protgs. Nos rsultats ont montr que le rpertoire des cellules T CD8 spcifiques est plus focalis que chez les patients protgs. En plus, nous avons observ que les clonotypes qui forment le rpertoire chez les patients protgs sont distincts de ceux chez les patients non-protgs. Ces clonotypes chez les patients protgs ont montr de plus grandes avidit et polyfonctionnalit que leurs homologues chez les patients non-protgs. En conclusion, nos rsultats suggrent que la protection contre le dveloppement dune infection chronique pendant lpisode de rinfection par le VHC est associe une augmentation de la magnitude, du spectre et de la fonctionnalit des rponses des cellules T spcifiques, ainsi qu un rpertoire des TCRs plus focalis compos des clonotypes distincts qui possdent de plus grandes avidit et polyfonctionnalit que chez les patients non-protgs. Lhomologie des squences des souches virales entre les diffrents pisodes de linfection est un dterminant majeur de ltablissement dune protection efficace. Ces rsultats ont donc des implications trs importantes pour le dveloppement dun vaccin prophylactique contre le VHC et dautres virus infection chronique.
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Le Costimulateur Inductible (ICOS) est un rcepteur exprim la surface des cellules T CD4 auxiliaires et T CD8 cytotoxiques. Il fut dmontr laide de modles murins de transplantation de moelle osseuse que ICOS joue un rle important dans linduction de la maladie du greffon contre lhte aigue (GVHD). ICOS potentialise deux signaux mdis par le rcepteur de cellules T (TCR) : lactivation de la phosphoinositide 3-kinase (PI3K) ainsi que la mobilisation interne de calcium. En conditions in vitro, dans les cellules CD4 et CD8, ICOS russi potentialiser le flux de calcium mdi par le TCR indpendamment de PI3K. La voie de signalisation de ICOS implique dans la GVHD demeure inconnue. Cependant, en utilisant une ligne de souris knock-in nomme ICOS-Y181F, dans laquelle le cellules T ont slectivement perdu la capacit dactiver PI3K par lentremise dICOS, nous avons dmontr que les cellules T peuvent utiliser un mcanisme ICOS indpendant de PI3K afin dinduire la GVHD. La mobilisation interne du Ca2+ mne lactivation de NFAT, un facteur de transcription cl rgulant des gnes comme IFN-, qui exprime une des cytokines cls impliques dans la GVHD. Nous mettons comme hypothse que la capacit pathognique intacte des cellules T ICOSY181F induire la GVHD, repose sur la signalisation du Ca2+ indpendante de PI3K. Le but de mon projet est didentifier les rsidus responsables de cette signalisation de Ca2+ mdie par ICOS ainsi que le mcanisme par lequel ce rcepteur fonctionne. laide de la mutagnse dirige, jai gnr des mutants dICOS et jai analys par cytomtrie en flux leur capacit activer le flux de Ca2+. Jai ainsi identifi un groupe de lysine sur la queue cytoplasmique dICOS situ proximit de la membrane comme tant essentiel la fonction de potentialisation du flux de Ca2+. Je fournis galement des preuves de limplication de la kinase Lck, membre de la famille de kinases Src, dans la voie de signalisation de ICOS mdiant la potentialisation du flux de Ca2+. Ainsi, ICOS sassocie Lck et mne une augmentation de lactivation de PLC1, la protine effectrice cl causant la sortie de Ca2+ de la rserve intracellulaire. En conclusion, notre tude permet de comprendre davantage une des voies de signalisation dICOS. Linflux de Ca2+ dans les cellules T implique la voie ICOS-Lck-PLC1. Une comprhension plus approfondie de cette voie de signalisation pourrait savrer bnfique afin dlaborer de nouvelles stratgies menant la prvention de maladies relies ICOS, comme la GVHD.
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MicroRNAs (miRNAs), an abundant class of ~22 nucleotide non-coding RNAs, are thought to play an important regulatory role in animal and plant development at the posttranscriptional level. Many miRNAs cloned from mouse bone marrow cells are differentially regulated in various hematopoietic lineages, suggesting that they might influence hematopoietic lineage differentiation. Some human miRNAs are linked to leukemias: the miR-15a/miR-16 locus is frequently deleted or down-regulated in patients with B-cell chronic lymphocytic leukemia and miR-142 is at a translocation site found in a case of aggressive B-cell leukemia. miR-181, a miRNA upregulated only in the B cell lineage of mouse bone marrow cells, promotes B cell differentiation and inhibits production of CD8 T cells when expressed in hematopoietic stem/progenitor cells. In contrast miR-142s inhibits production of both CD4 and CD8 T cells and does not affect B cells. Collectively, these results indicate that microRNAs are components of the molecular circuitry controlling mouse hematopoiesis and suggest that other microRNAs have similar regulatory roles during other facets of vertebrate development.
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Spleen or spleen plus bone marrow cells from (BALB/c x C57Bl/6)F1 donors were transferred into BALB/c recipients 21 days before skin or cardiac transplantation. Prolonged graft survival was observed on recipients treated with the mixture of donor-derived cells as compared to those treated with spleen cells alone. We evaluated the expression of CD45RB and CD44 by splenic CD4(+) and CD8(+) T cells 7 and 21 days after donor cell transfer. The populations of CD8(+)CD45RB(low) and CD8(+)CD44(high) cells were significantly decreased in mice pre-treated with donor spleen and bone marrow cells as compared to animals treated with spleen cells only, although these cells expanded in both groups when compared to an earlier time-point. No differences were observed regarding CD4+ T cell population when recipients of donor-derived cells were compared. An enhanced production of IL-10 was observed seven days after transplantation in the supernatants of spleen cell cultures of mice treated with spleen and bone marrow cells. Taken together these data suggest that donor-derived bone marrow cells modulate the sensitization of the recipient by semi-allogeneic spleen cells in part by delaying the generation of activated/memory CD8(+) T cells leading to enhanced graft survival. (c) 2007 Elsevier B.V. All rights reserved.
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Toll-like receptors (TLRs), a family of mammalian receptors, are able to recognize nucleic acids. TLR3 recognizes double-stranded (ds)RNA, a product of the replication of certain viruses. Polyinosinic-polycytidylic acid, referred to as poly(I:C), an analog of viral dsRNA, interacts with TLR3 thereby eliciting immunoinflammatory responses characteristic of viral infection or down-regulating the expression of chemokine receptor CXCR4. It is known that dsRNA also directly activates interferon (IFN)-induced enzymes, such as the RNA-dependent protein kinase (PKR). In the present study, the mRNA expression of TLR3, CXCR4, IFN gamma and PKR was investigated in a culture of peripheral blood mononuclear cells (PBMCs) stimulated with poly(I:C) and endogenous RNA from human PBMCs. No cytotoxic effect on the cells or on the proliferation of CD3(+), CD4(+) and CD8(+) cells was observed. TLR3 expression in the PBMCs in the presence of poly(I:C) was up-regulated 9.5-fold, and TLR3 expression in the PBMCs treated with endogenous RNA was down-regulated 1.8-fold (p=0.002). The same trend was observed for IFN gamma where in the presence of poly(I:C) an 8.7-fold increase was noted and in the presence of endogenous RNA a 3.1-fold decrease was observed. In the culture activated with poly(1:C), mRNA expression of CXCR4 increased 8.0-fold and expression of PKR increased 33.0-fold. Expression of these genes decreased in the culture treated with endogenous RNA when compared to the culture without stimulus. Thus, high expression of mRNA for TLR3, IFN gamma, CXCR4 and PKR was observed in the presence of poly(I:C) and low expression was observed in the cells cultured with endogenous RNA. In conclusion, TLR3 may play major physiological roles that are not in the context of viral infection. It is possible that RNA released from cells could contain enough double-stranded structures to regulate cell activation. The involvement of endogenous RNA in endogenous gene expression and its implications in the regulation thereof, are still being studied, and will have significant implications in the future.
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Fundao de Amparo Pesquisa do Estado de So Paulo (FAPESP)
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Fundao de Amparo Pesquisa do Estado de So Paulo (FAPESP)
