They are made available as submitted by the authors. “
“In the present study, the relationship between exopolysaccharide production and cholesterol removal rates of five strains of Lactobacillus delbrueckii subsp. bulgaricus isolated from home-made yoghurt was studied. Test strains were selected according to their exopolysaccharide production capacity. Influence of different bile concentrations on cholesterol removal was investigated. It was confirmed that B3, ATCC 11842 and G11 strains which produce high amounts of exopolysaccharide (211, 200 and 159 mg/l, respectively)

were able to remove more cholesterol from the medium compared to those that produce low amounts of exopolysaccharide (B2, A13). The highest cholesterol removal (31%) was observed by strain L. delbrueckii subsp. bulgaricus B3, producing a high amount of exopolysaccharide, in 3 mg/ml bile concentration. Cholesterol removal by resting and dead cells was investigated Selleck Cisplatin and it was found to be 4%–14% and 3%–10%, respectively.

Cholesterol removal by immobilized and free cells of the B3 strain was studied and it was determined that immobilized cells are more effective. Influence of cholesterol on exopolysaccharide production has also been tested and it was found that cholesterol increased EPZ-6438 supplier the production of EPS. The results indicated that: (i) there is a correlation between cholesterol removal and EPS production; and (ii) L. delbrueckii subsp. bulgaricus B3 is regarded as a suitable Celecoxib candidate probiotic and adjunct culture. Probiotics are viable microorganisms that exhibit beneficial effects on the health of the host when they are ingested (1). Lactobacillus spp. and Bifidobacterium spp. are the most commonly studied probiotic

bacteria. They cause reduced lactose intolerance, increased immune responses, and lowered blood cholesterol, and are beneficial in the alleviation of some diarrheas and prevention of cancer (2). Certain strains of lactic acid bacteria (LAB) are able to synthesize EPS that are secreted into their environment, as in milk (3). The bacterial EPS are not used as energy sources by producer microorganisms. Besides their ecological functions and technological significance in the production of several fermented dairy products, EPS have been claimed to have antitumor effects and immunostimulatory activity and to lower blood cholesterol (4, 5). Cholesterol is an important basic building block for body tissues. However, elevated blood cholesterol is a well-known major risk factor for coronary heart diseases (6). Several studies have indicated that consumption of certain cultured dairy products reduce serum cholesterol (7, 8). Therefore, interest in the use of probiotics for lowering blood cholesterol levels has been increasing. However, the mechanisms by which the organisms remove the cholesterol from the laboratory media are not completely clear (9).

For the triple regimens, analyses of the challenge virus loads were carried not only in splenocytes, where respective 2.7- and 5.5-fold decreases were detected for the DCM and DMC regimens (Fig. 4D), but also in the pooled superficial cervical and

MLNs and thymus. In all of these nonsplenic sites, a considerable clearance of the EcoHIV/NDK virus was detected (Fig. 4E). At 42 days postvaccination, in vivo killing of AMQ peptide-pulsed click here and re-infused splenocytes showed close to 100% killing efficiency by T cells elicited by both triple regimens (Fig. 4F). Finally, to assess the longevity of the triple vaccine-induced responses, the third subgroup of animals receiving either the DCM or DMC regimens was rested for 115 days prior to the late surrogate virus challenge. Collected pooled PBMCs maintained polyfunctionality upon the AMQ peptide restimulation and the IFN-γ+-cell frequencies remained at respective 5.6 and 2.2% of total CD8+ cells for the DCM and DMC regimens (Fig. 5A). After challenge and measured in spleen, these frequencies rose to means of 9.6 and 6.7%, respectively (Fig. 5B). In the same animals, the DCM- and DMC-induced memory T cells decreased the EcoHIV/NDK DNA copy numbers 3.5-

and 5.2-fold, respectively. Using ANOVA analysis, the means of the challenge virus loads among individual treatments were significantly different, but in pairwise comparisons, this significance was lost after the Bonferroni adjustment (Fig. 5C). Thus, a sequential combination of three different vaccine modalities into a single regimen induced robust, durable, and polyfunctional CD8+ selleck screening library T-cell responses. It remains that the real benefit of triple regimens may only become apparent in more challenging situations such as protection of humans against HIV-1. Finally, we assessed the AMQ-specific,

IFN-γ-producing CD8+ T cells for expression of proliferation-promoting IL-2, L-selectin CD62L, memory marker many IL-7 receptor α-chain CD127 and CD27, which is required for generation and maintenance of T-cell immunity and is lost from terminally differentiated effector cells. Central memory (TCM), but not effector memory (TEM), T cells possess ability to express high levels of CD62L, have a high proliferative potential, and are primarily found in lymphoid tissue. Thus in spleen for both DCM and DMC regimens, the AMQ-specific postchallenge responses increased from the peak to the memory phase for IL-2 production and CD62L and CD127 expression (Fig. 6A). Memory PBMCs prior to the challenges differed from immune splenocytes the most in lower levels of IL-2 and higher expression of CD62L and CD27 (Fig. 6B). In addition to memory markers, vaccine-elicited CD8+ T cells were also analyzed for expression of the α4β7 adhesion molecule linked to migration of lymphoytes to the GALT. Vaccine-induced T-cell population expressing low level of α4β7 was found among immune splenocytes (Fig. 6C), but not PBMCs (Fig. 5D).

Obviously, it will

not only be the targeted gene that is investigated, but the entire linked fragment, containing thousands of polymorphic nucleotides affecting protein structure and expression. The optimal solution is, of course, to use a mouse that is genetically identical to the used ES cell. There are now ES cells available from different strains, derived from substrains of 129, Balb/c, DBA/1 or C57Bl6/N, although the most commonly used strain is still 129. Remarkably, it has not been possible to make ES cells from the most commonly used standard strain, i.e. C57Bl6/J, instead the existing ES cells said to be from B6 are contaminated with other strains. For example, the commonly used Bruce ES cell Cilomilast molecular weight 9, believed to be derived from B6, differs from C57Bl6/J by 6.4% of 10 000 investigated single nucleotide polymorphisms (SNPs) (Holmdahl et al., unpublished data). Recently, ES cells from the C57Bl6/N background 10 have been established but it must be remembered that the C57Bl6/N mouse differs significantly both genetically Stem Cell Compound Library and phenotypically from, for example, the C57Bl6/J strain

10, possibly due to contaminating genes from the Swiss mouse. In most cases, however, it is not possible to use mice with ES cell identity. Such experiments will not be conclusive but are nonetheless valuable if supporting functional evidence is provided or if the phenotype is qualitative rather than quantitative; however, it is reasonable to expect that in such cases the borders of

the linked fragment are reported to provide the reader sufficient information to judge the results. Genotyping the fragment is standard technology today, and it is possible to have this done as a service. However, there are additional pitfalls. A major problem in many publications concerns the genetic background of the proband mice compared with that of control mice, a problem that is occasionally exposed by way of a debated controversy 11, 12. Backcrossing a targeted gene to the control mouse background even with ten generations of backcrossing, which seem to be the informal standard of today, does not necessarily clean up the genetic background. Small fragments may still remain due, for example, to selection of breeding performance or just by chance. BCKDHA We have screened more than twenty 10n backcrossed strains with a specifically designed 10k SNP chip 13 and found that almost half of these strains still contained detectable fragments originating from the donor. Even more disturbing is that the control strain used in many published papers is not in fact identical to that used for the backcrossing. In these cases, the control strain is selected from a parental colony in the same animal house or, worse, from another animal house or from a commercial supplier; the selected strain may only share the genealogic name of the strain.

Necrosis and kidney damage were assessed with H&E-stained kidney tissue 24 h after transplantation. Acute tubular necrosis score (ATN) was decreased significantly in the immunosuppressive treatment group compared with the control group (4 ± 0·63

in control; rapamycin 2·2 ± 0·41; FK506 2 ± 0·63; rapamycin + FK506 1·2 ± 0·41; P < 0·001 versus control; Fig. 2a). Figure 2b Birinapant clinical trial shows a representative image of H&E stain for the evaluation of renal injury in each treatment group. The use of rapamycin plus tacrolimus (group 4) was associated with a lower level of acute tubular necrosis (ATN) compared with rapamycin alone (P < 0·05), but no statistical difference was observed in comparison with tacrolimus. Also, the number of apoptotic nuclei in renal medulla was determined as evidence of kidney injury. In the control group, the number of TUNEL-positive cells was higher compared with the immunosuppressive treatment groups (control: 138·7 ± 24·8; rapamycin: 22·3 ± 4·5; FK506: 54·8 ± 8·3 and rapamycin + FK506: 17·5 ± 5; P < 0·001 versus control, Fig. 3a and b). As normal kidney control, the number of positive apoptotic nuclei in sham animals was lower than 6/mm2 located only in deep medullary epithelial tubules (data not shown). The use of rapamycin alone or rapamycin plus tacrolimus showed a lower number of apoptotic nuclei cells with respect to

tacrolimus treatment (P < 0·05 and P < 0·01, respectively). Finally, a statistically significant difference in the expression of Bcl2 was detected in BMN-673 kidney tissue by immunohistochemistry. In accordance with our previous results, Bcl2 levels in the control group were lower than in the immunosuppressive treatment group (control: 1·8 ± 0·5; rapamycin: 16·01 ± 4; FK506: 5-Fluoracil molecular weight 9 ± 2·6 and rapamycin + FK506: 6 ± 1·25; P < 0·01 and P < 0·05 versus control, respectively)

(Fig. 3c). These results suggest that preconditioning of the donor with rapamycin and tacrolimus or a combination of both is associated with lower kidney damage after transplantation. In order to determine if the immunosuppressive treatment affected the complement function, the C3 levels in recipient animals were assessed. C3 plasma values in immunosuppressive treatment were significantly lower than control group levels (control: 495 ± 94 pg/ml; rapamycin: 166·7 ± 57·1 pg/ml; FK506: 165 ± 66·3 pg/ml and rapamycin + FK506: 103·3 ± 33·3.; P < 0·001 versus control, Fig. 4a). No differences were found among the various immunosuppressive treatment groups (P > 0·05). In addition, the local expression of C3 within the grafts was analysed. Immunohistochemical analysis of graft tissue 24 h after transplantation revealed that local expression of C3 was higher in the control group compared with the immunosuppressive treatment group (control: 53·98 ± 4·5; rapamycin: 10·62 ± 3·2; FK506: 2·27 ± 0·7 and rapamycin + FK506: 1·58 ± 0·54.

Increased nitric oxide (NO) production and phosphorylation level of endothelial nitric oxide synthase (eNOS) were measured in HUVECs following CRT stimulation, while the total eNOS expression was not significantly changed. Furthermore, CRT promoted the proliferation, migration and tube formation of HUVECs, which were significantly inhibited by a specific eNOS inhibitor. These findings suggested that CRT may be involved in angiogenesis events in RA through NO signalling pathways, which may provide a potential therapeutic target in the treatment of RA. “
“Mammalian ortholog of Drosophila cell

polarity protein, Dlg1, plays a critical role in neural synapse formation, epithelial cell homeostasis, and urogenital MK0683 price development. More recently, it has been proposed that Dlg1 may also be involved in the regulation of T-cell proliferation, migration, and Ag-receptor signaling. However, a requirement for Dlg1 in development and function of T lineage cells remains to be established. In this study, we

investigated a role for Dlg1 during T-cell development and function using a combination of conditional Dlg1 KO and two different Cre expression systems where Dlg1 https://www.selleckchem.com/products/AZD2281(Olaparib).html deficiency is restricted to the T-cell lineage only, or all hematopoietic cells. Here, using three different TCR models, we show that Dlg1 is not required during development and selection of thymocytes bearing functionally rearranged TCR transgenes. Moreover, Dlg1 is dispensable in the activation and proliferative expansion of Ag-specific TCR-transgenic CD4+ and CD8+ T cells in vitro and in vivo. Surprisingly, however, we show that Dlg1 is required for normal generation of memory T cells during endogenous response to cognate Ag. Thus, Dlg1 is not required for the thymocyte selection or the activation

of primary T cells, however it is involved in Casein kinase 1 the generation of memory T cells. Cell polarity genes are involved in the maintenance of cellular architecture of epithelial cells, control of cell proliferation, migration and differentiation during physiological tissue renewal. Three polarity protein complexes have been described: the Par complex (Par3, Par 6, and atypical protein kinase C (aPKC)), the Crb complex (which includes Crb protein, PALS1, and PATJ), and the Scrib complex consisting of Scribble, Lgl, and Dlg proteins. These polarity complexes are thought to act antagonistically with each other and to interact with both the cytoskeleton and signal transduction network [1]. Mammalian discs large proteins (Dlg1/Sap97, Dlg2/PSD-93, Dlg3/Sap102, and Dlg4/PSD-95) belong to a family of membrane-associated guanylate kinases characterized by the presence of three PSD-95, discs large, ZO-1 (PDZ) domains, an SH3 domain, and a guanylate kinase domain.

The mechanisms behind the extreme sensitivity and specificity of such broadly reactive receptors are intriguing and will likely be important to understand antigen receptor function in immune responses and in abnormal check details processes such as autoimmunity or

lymphocyte cancers. In their architecture, antigen receptors are multichain complexes. They contain the clonotypic antigen-binding chains (TCR-α and TCR-β chains or BCR immunoglobulin (Ig) heavy and light chains) and constant signalling chains (two CD3 dimers and one TCR-ζ dimer for the TCR, the Ig-αβ heterodimer for the BCR).1,2 The first detectable biochemical step of antigen receptor activation is tyrosine phosphorylation of the cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs) by Src family kinases. The initial phosphorylation leads to recruitment of Syk/ZAP70 kinases, their substrates and signalling enzymes that eventually bring about lymphocyte activation. The exact mechanisms by which antigen binding

triggers these biochemical steps are highly debated and have been the subject of a number of excellent reviews.3–7 In vivo, lymphocytes continuously scan tissues for the presence of antigen displayed on antigen-presenting cells (APCs). Landmark imaging of T cells interacting with APCs revealed that T cells form a specialized contact with the APCs, called the immunological synapse.8,9 The synapse is characterized by accumulation of the TCR in the centre, MK0683 nmr with a surrounding ring of adhesion molecules. This pattern of receptor organization

was later extended to B cells10 and cytotoxic T cells11 and suggested that spatial organization in the immunological synapse may provide MycoClean Mycoplasma Removal Kit a common layer of fidelity for lymphocyte activation.12,13 Imaging of the formation of the immunological synapse showed that the accumulation of antigen receptors in the centre of the synapse is preceded by microclustering of the antigen receptors in the periphery (Fig. 1).14–16 Once formed, the microclusters are transported to the centre of the synapse by an actin-dependent process. The synaptic microclusters appear to be the platforms for receptor activation and signal propagation. For example, microclusters recruit signalling molecules such as Src kinases and ZAP-70/Syk. They also exclude inhibitory phosphatases such as CD45. However, many of the molecular mechanisms of antigen receptor activation inside these structures remain beyond the resolution of optical microscopy and could not be directly addressed by conventional imaging.7,17 Recently, several techniques based on fluorescence microscopy offer imaging with resolution that approaches the molecular scale (5–40 nm).18–20 The most accessible of these new techniques have been photoactivated localization microscopy (PALM)21 and the related stochastic optical reconstruction microscopy (STORM),22 which are based on the detection and precise localization of single molecules.

The segments of genomic DNA of strain NUM 1720T encoding the DNA gyrase

β-subunit (gyrB) and the RNA polymerase β-subunit (rpoB) gene were amplified by PCR and sequenced. The gyrB and rpoB primers were designed based on an alignment of the nucleotide sequence of each gene from S. ficaria. The gyrB and rpoB sequences used for the phylogenetic studies were obtained from the DDBJ and GenBank databases. DNA-DNA hybridization was performed fluorometrically by the method of Ezaki et al. (8) using photobiotin-labelled DNA probes and microdilution wells. A heat-denatured sample of DNA (1 μg) was immobilized in each well of a microplate (Immuno plate II; Nunc, selleck chemicals llc Roskilde, Denmark) at 30°C for 2 hr. The microplate was dried at 45°C for 2 hr and then photobiotin-labelled heat-denatured probe DNA (0.125 μg per well) was used for the hybridization (incubated at 46.8°C for 3 hr). Other procedures were conducted according to the original instructions. The guanine-plus-cytosine (G + C) contents of the DNA preparations were determined LY294002 price by the (HPLC) method (9). Biochemical analysis was conducted using the API

50 CH and API ZYM (Biomérieux, Marcy l’Etoile, France) system according to the manufacturers’ instructions. For quantitative analysis of the cellular fatty acid composition and isoprenoid quinone analysis, cells were harvested from an NG agar (l−1:8.0 g nutrient broth, 8.0 g glucose, 5.0 g NaCl, 0.5 g yeast extract) incubated at 30°C for 2 days as described by Ajithkumar et al. (10). Fatty acid methyl esters were prepared and Clomifene identified by following the instructions of the Microbial Identification

system, as described by Sasser (11). Isoprenoid quinones were extracted from lyophilized cells and subjected to HPLC as described previously (12). The partial nucleotide sequences of the 16S rRNA, gyrB and rpoB genes from strain NUM 1720T were determined and phylogenetic trees based on these data were constructed by the neighbor-joining method. The 16S rRNA gene sequence of NUM 1720T showed 99.4%, 97.2%, 97.2% and 97.1% similarity to those of G. quercinecans, P. rwandensis, S. ficaria and K. ascorbata, respectively. The phylogenetic tree of 16S rRNA gene sequence (Fig. 1) showed that strain NUM 1720T was related most closely to G. quercinecans. The gyrB gene sequence of strain NUM 1720T showed 98.0%, 87.4%, 86.8% and 86.8% similarity with those of G. quercinecans, Serratia rubidaea, Serratia odorifera and Serratia grimesii. The rpoB gene sequence of strain NUM 1720T showed 98.2%, 93.2%, 93.0% and 92.6% similarity to those of G. quercinecans, Serratia. nematodiphila, S. ficaria and Serratia. marcescens subsp. marcescens. The gyrB and rpoB gene trees showed similar topologies and a close phylogenetic relationship between strain NUM 1720T and G. quercinecans (Fig. 2, 3).

Thus, we do not exclude that, in SN-APS GDC-0449 in vitro patients, phospholipid-binding proteins may also be involved in anti-phospholipid reactivity, as TLC immunostaining does not exclude this possibility. However, at present the involvement of phospholipid-binding proteins other than annexin II remains unclear. Because, in recent years, our research has focused on the identification

of endothelial autoantigens involved in different autoimmune diseases, studies based on the screening of endothelial cDNA expression libraries also identified vimentin as a new phospholipid-binding protein autoantigen in SN-APS [7]. Interestingly, in almost all the patients the positive result obtained by TLC assay was confirmed with the second result after at least 12 weeks; conversely, two patients negative with the first sample displayed aPL reactivity with the second sample. Of note, one of the last such cases was a 26-year-old female with INK 128 molecular weight SLE and proteinuria; histological evaluation of the kidney biopsy showed diffuse global lupus nephritis (class IV-G) associated with thrombotic microangiopathy suggestive of APS. Recently, it was demonstrated that aPL may exert

their pathogenic role by triggering a signal transduction pathway involving IRAK phosphorylation, NF-κB activation and translocation with consequent release of proinflammatory and procoagulant factors by endothelial and/or monocytic cells [18,20,25]. In order to verify the possible pathogenic role of the autoantibodies we demonstrate that purified IgG from sera of SN-APS patients induce IRAK serine phosphorylation with consequent NF-κB activation. Interestingly, we demonstrated that aCL as well as aLBPA were involved in this signalling pathway triggering, as these autoantibodies failed to induce however IRAK phosphorylation if they were

previously adsorbed with highly purified aCL or LBPA. Previous studies demonstrated that aPL induce monocyte and endothelial cell TF expression through the simultaneous activation of NF-κB-related proteins as well as aPL induce VCAM-1 on endothelial cells surface and that these effects are correlated with increased adhesion of leucocytes to endothelium [18,25,26]. According to these findings we demonstrate that IgG from SN-APS patients triggering resulted in the expression of VCAM-1, as well as release of TF from endothelial cells, which may contribute to the pathogenesis of thrombosis in patients with APS. Deep vein thrombosis, myocardial infarction and stroke are the major causes of morbidity and death among APS patients due to the high risk of recurrence; therefore, it is mandatory to identify among patients with suspected APS repeatedly negative for conventional aPL tests, those with a true APS to offer them long-term anti-coagulation, as widely recommended for secondary thromboprophylaxis in this disease [27,28].

3 domain solely affects JNK1 signaling in T cells. Next, IP-FCM analyses of lysates from T cells stimulated in the presence of Tat-POSH were performed

to map the composition of the POSH/JIP-1 scaffold complex. Tat-POSH disrupted approximately 30% of POSH/JIP-1 complexes over the first 48 h of stimulation (Fig. 2E). In the presence of Tat-POSH, Rac-1, the MAP3K proteins, MLK-3 and Tak1, were not significantly reduced in Co-IP with POSH, while MKK7 and JNK1 were not affected in Co-IP with JIP-1 (Fig. 2E and Supporting Information click here Fig. 2). This suggests POSH binds Rac-1 and MLK-3 and the SH3.3 domain of POSH associates with the JIP-1/MKK7/JNK1 complex to assemble the JNK1 signaling module in CD8+ T cells (Fig. 2E and [26]). JNK1 is important for CD8+ T-cell proliferation, regulates entry into cell cycle, and plays a major role in initiating apoptosis [10]. First, we determined the effect of uncoupling POSH from JIP-1 on proliferation. Naïve OT-I T cells stimulated with OVAp-pulsed APC in

the presence of Tat-POSH exhibited significant reduction in the number of divisions (Fig. 3A). T cells stimulated in the presence Tat-POSH had reduced induction of CD25 (Fig. 3B). Importantly, this defect was not recovered in the presence of excess IL-2 and/or IL-12 (data not shown). Next, we determined whether these defects in proliferation were the result of fewer cells entering cell cycle or increased apoptosis. The percent of cells in cell cycle, as Leukotriene-A4 hydrolase measured by the Ki-67 [38], was significantly reduced in the presence of PARP inhibitor cancer Tat-POSH (Fig. 3C). However, there was no statistical difference in the percent of cells undergoing apoptosis, as measured by cleaved caspase-3, 7-AAD, or annexin-V (Fig. 3D, data not shown). Remarkably, these data closely resemble observations from JNK1−/− CD8+ T cells [10, 17] and support the role of the POSH/JIP-1 scaffold network in regulating JNK1-induced proliferation. JNKs are important in the differentiation and development of effector function of CD8+ T cells. JNK1 positively regulates IFN-γ, perforin, and TNF-α expression [17, 18, 39], while JNK2 inhibits IFN-γ and

granzyme B induction [16, 19]. To test the role of the POSH/JIP-1 scaffold complex on the induction of these effector molecules, OT-I T cells were stimulated with OVAp-pulsed APC in the continuous presence of Tat-POSH or Tat-control. Four days after stimulation, cells were washed and restimulated in the presence of Brefeldin A (without additional Tat-POSH) and then assessed for effector molecule expression by intracellular staining. Cells initially stimulated in the presence of Tat-POSH had a significant reduction in both the percentage of IFN-γ+ cells and amount of IFN-γ produced on a per-cell basis (Fig. 4A). Importantly, this was independent of cell division as significantly fewer of even the most divided Tat-POSH-treated cells produced IFN-γ (Fig. 4B). FasL induction was also significantly decreased (Fig.

Even though testing for DTH response cascades in-vitro is limited by default, the use of some key elements of the former DTH skin test in this new cytokine release assay might help to fill the gap left following the discontinuation of the classical DTH skin test. Also, because of its standardization and simplicity, it may be a particularly suitable research tool in the field of psychoneuroendocrinology in clinical, as well as under extreme field conditions, such as in space flight experiments. The authors are grateful for the intramural, institutional support of the Department of Anaesthesiology.

The experimental part of the study using the model of parabolic flights was supported generously by a grant from the German National Space Program by the German Space learn more Agency (DLR) on behalf of the Federal Ministry of Economics and Technology (BMWi 50WB0523 and 50WB0719) and was also supported by the European Space Agency (ESA) and the Centre National d’Etudes Spatiales (CNES). The authors

thank all the volunteers, who participated with extreme professionalism in this study, and extend their appreciation to the efficient support from DLR (Dr U. Friedrich, Dr H.-U. Hoffmann) and NOVESPACE (F. Gai) during preparation and performance of this investigation. Selleck Inhibitor Library This investigation is part of the MD theses of Markus Gruber and Florian Muckenthaler. W.M. is affiliated to Immumed Inc., a laboratory for applied immunology offering a testing service for immunological parameters to commercial, medical and research clients. “
“CD4+ T cells are important effectors of inflammation and tissue destruction in many diseases of immune dysregulation. As memory T cells develop early during the preclinical stages of autoimmune and inflammatory diseases, immunotherapeutic approaches to treatment of these diseases,

once established, must include the means to terminate memory T-cell responses. Traditionally, it has been considered that, due to their terminally differentiated nature, memory Mannose-binding protein-associated serine protease T cells are resistant to tolerance induction, although emerging evidence indicates that some immunotherapeutic approaches can terminate memory T-cell responses. Here, we demonstrate that CD4+ memory T-cell responses can be terminated when cognate antigen is transgenically expressed in steady-state DC. Transfer of in-vitro-generated CD4+ memory T cells establishes, in nontransgenic recipients, a stable and readily recalled memory response to cognate antigen. In contrast, upon transfer to mice expressing cognate antigen targeted to DC, memory CD4+ T cells undergo a phase of limited proliferation followed by substantial deletion, and recall responses are effectively silenced. This finding is important in understanding how to effectively apply immunotherapy to ongoing T-cell-mediated autoimmune and inflammatory diseases.