Modifying the classical suppression PD-0332991 nmr assay to measure cytokine production by the responder (CD4+CD25–) T cells activated has revealed that there may be a hierarchy of suppression, with down-regulation of IFN-γ mRNA occurring earlier than suppression of Th2 cytokine production [79]. A similar study examining the transcriptional profile of T cells activated in the presence or absence of Tregs revealed down-regulation of factors promoting both Th1 and Th2 development [IL-12Rα, IL-12Rβ2 and Irf-4 as well as T-bet and GATA binding

protein 3 (GATA-3)] in ‘suppressed’ T cells [80]. Notably, expression of IL-21, a Th17-associated cytokine, was also suppressed upon co-culture, suggesting that Tregs can down-regulate at least one element of Th17 effector function. Sakaguchi

et al. reported that mice lacking CD25+ T cells develop exacerbated responses to non-self antigens and eventually develop various autoimmune selleck chemical pathologies [13]. This seminal observation implicated Tregs in governing the magnitude of immune responses and setting the threshold for the development of clinical autoimmune disease. If Tregs are particularly important in restraining one type of effector T cell response, this might be revealed by looking at what type of pathology is most prevalent in the absence of Tregs or when their regulatory function is impaired. aminophylline Several mouse models have been utilized to investigate defects in FoxP3 function with varied degrees of severity, from global impairment [18,81,82] and inducible ablation [34], to attenuated expression of FoxP3 [35], to Treg specific-disruption of selected suppressive mechanisms [30,31] or homing mechanisms [29]. T cells from scurfy mice are hyperproliferative to TCR ligation [17] and produce higher levels of cytokines than wild-type littermates [83]. Heightened production of IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IFN-γ and TNF-α in scurfy mice

indicated that components of both Th1 and Th2 responses are exacerbated in the absence of functional Tregs, while pathology results from an excessive ‘non-polarized’ response. Because IL-17 was not recognized as an important proinflammatory product of T cells at the time the scurfy mouse was characterized, levels of IL-17 were not determined. Mice with a targeted disruption of FoxP3 recapitulated the phenotype of scurfy mice displaying allergic airway inflammation and hyperproduction of immunoglobulin (Ig)E, indicative of overactive Th2 responses. However, both Th1 and Th2 cytokines were overproduced in FoxP3 knock-out mice, suggesting a non-selective dysregulation of both Th1 and Th2 responses [82].

Different automated immunostaining systems showed similar results. 21 of 186 samples had nuclear accumulation in ≥5% of cells, 17 samples showed <5% ß-catenin positive nuclei. None of these 17 cases had CTNNB1 mutations, but 18 of 21 cases with ≥5% accumulation did, identifying these 18 cases as Wnt-subgroup medulloblastomas. 15 of 18 mutated cases showed monosomy 6, 3 had balanced chromosome 6. On the contrary, none of the CTNNB1 wildtype tumors had monosomy 6. Standard neuropathological evaluation of medulloblastoma samples should include

IHC of ß-catenin because tumors with high nuclear accumulation of ß-catenin most probably belong to the Wnt subgroup of medulloblastomas. Still, IHC alone may be insufficient to detect all Wnt cases. Similarly, chromosome 6 aberrations were not present in all CTNNB1-mutated cases. Therefore, we conclude that sequencing analysis

of CTNNB1 exon Carfilzomib ic50 3 in combination with ß-catenin IHC (possibly as pre-screening method) is a feasible and cost-efficient way for the determination selleck of Wnt medulloblastomas. “
“Pineal parenchymal tumors (PPTs) are rare neoplasms which occupy less than 1% of primary CNS tumors. Because of their rare incidence, previous reports on PPTs are limited in number and the useful molecular markers for deciding histological grading and even selecting chemotherapy are undetermined. In this study, we conducted immunohistochemical

analysis of 12 PPT specimens, especially for expression of O6-methylguanine DNA methyltransferase (MGMT) to assess whether temozolomide (TMZ) could serve as a possible alternative therapy for PPTs. We analyzed 12 PPTs, consisting of three pineocytomas, six PPTs of intermediate differentiation (PPTIDs), and three pineoblastomas. Org 27569 Immunohistochemical analysis was performed using antibodies against MGMT, synaptophysin, neurofilament protein (NF), p53, and neuronal nuclear antigen (NeuN). Immunohistochemically, 11 out of 12 cases were positive for MGMT. The mean MIB-1 labeling index was less than 1% in pineocytoma, 3.5% in PPTID, and 10.5% in pineoblastoma. All 12 cases were positive for synaptophysin and 11 cases, except one PPTID case, showed positive for NF. Nuclear staining of NeuN was negative in all cases although cytoplasmic staining of NeuN was observed in five cases. No case was positive for p53. Eleven out of 12 cases of PPTs demonstrated MGMT expression, suggesting chemoresistancy to TMZ treatment. This is the first report showing MGMT expression in PPTs. In addition, MIB-1 labeling index correlated with WHO grade, although the immunoreactivity of synaptophysin, NF, NeuN and p53 did not correlate with the histological grade. “
“A. Morancho, L. García-Bonilla, V. Barceló, D. Giralt, M. Campos-Martorell, S. Garcia, J. Montaner and A.

These data confirm and extend previous work showing that C3/C4- or FcγR-deficient mice cleared high-dose LCMV WE infection with the same kinetics as wild-type mice [9]. In contrast to these findings, the antiviral activity of nonneutralizing LCMV GP specific Abs has been shown to be dependent on complement [28]. These data were derived from a B-cell receptor transgenic model based on the “neutralizing” LCMV GP specific mAb KL25 and viral Ab escape

variants. Antiviral activities of nonneutralizing learn more Abs are well known and have been demonstrated in many other infection models [29-39]. Such Abs may function autonomously [40, 41] or in conjunction with host components such as the complement system or FcγR-bearing cells [42-48]. In all of these studies, the Abs were directed against viral envelope proteins expressed at high

levels on the surface of virions or infected cells. This is distinct from our conditions analyzing the role of Abs specific for an internal viral protein that is predominantly present inside of virions and infected cells. Antigen-IgG immune complexes are known to enhance T-cell priming by induction of dendritic cell selleck chemical maturation and improved antigen presentation [49]. Short passive immunotherapy with neutralizing Abs has further been shown to enhance the CTL responses in mice infected shortly after birth with an ecotropic retrovirus derived from Friend murine leukemia virus [19]. In our experimental system, L-gulonolactone oxidase transfer of LCMV immune serum did not increase the LCMV-specific CTL response rendering it unlikely that that the accelerated virus

elimination we observed was due to increased CD8+ T-cell priming. There is no doubt that T cells are essential for immunity against non- or poorly cytopathic viruses such as HCV or HIV in humans or LCMV in mice and that Abs on their own are unable to combat these infection. Nonetheless, our study performed in a prototypic CD8+ T-cell-controlled virus infection model unravels a role for nonneutralizing Abs specific for an internal viral protein. As exemplified with our experiments, these Abs generated in the early phase of the infection may shift the delicate balance from insufficient virus elimination and T-cell exhaustion to virus control and memory T-cell formation. In the accompanying publication by Richter and Oxenius [50], LCMV binding but nonneutralizing Abs were also shown to protect mice from chronic LCMV infection independently of activating FcγR or C3 complement. In this context, it is noteworthy that Ab-dependent cell-mediated cytotoxicity and not broadly neutralizing Ab or T-cell responses correlated with protective activity in the HIV-1 vaccine trial RV144 [51]. Our study encourages attempts to examine the role of nonneutralizing Abs specific for internal viral proteins also in viral infections in humans that often lead to pathogen persistence and T-cell exhaustion. C57BL/6J (B6), SWISS, and NMRI mice were obtained from Janvier.

The results of the present study support this. Although retrospective, our study provides valuable clinical information. Several clinical trials are ongoing to find new and efficient treatment opportunities for vasculitis, but we meet daily patients who are in need of cure and do not meet the inclusion criteria for such studies. Therefore, an analysis and long-term follow-up of patients treated off label with RTX, such as PD-1/PD-L1 assay in our cohort, contribute to a better appraisal of the therapeutic effects of RTX in ANCA-associated vasculitic manifestations. In conclusion, based on our cohort of 29 patients with ANCA-associated vasculitis, we observed the best additive effect of RTX treatment in patients with

vasculitic manifestations in the Selleckchem Sunitinib kidneys and lung granulomatosis, whereas granulomatous lesions in the bronchi, trachea and subglottic stenosis seem to be more resistant to the effect of RTX treatment. Although treatment with RTX has become a therapeutic alternative for ANCA-associated vasculitis, further studies are warranted to assess the effect of RTX treatment on diverse vasculitic and granulomatous manifestations in different organs. This work was supported by grants from the Gothenburg Medical Society, the Swedish Medical Society, the Swedish Association against Rheumatism,

the Gothenburg Association against Rheumatism, the King Gustaf V foundation, the Swedish Medical Research Council, the Nanna Niclosamide Svartz Foundation, Rune and Ulla Amlövs Foundation, St. Family Thölens and Kristlers Donations Foundation and the University of Gothenburg. The authors do not have any financial or other relationship that might lead to a conflict of interest. Figure S1 Changes in arbitrary sinus obliteration score after RTX treatment. Figure S2 The effect of RTX treatment on circulating immunoglobulin producing cells and serum immunoglobulin levels. Table S1 Characteristics of RTX treated patients with kidney involvement. Table S2 Characteristics of RTX treated patients with involvement of lower and upper airways. Apeendix S1 Supplementary methodology. “
“HIV replication is restricted by some anti-CD4 mouse mAb in vitro and in vivo. However, a human monoclonal anti-CD4 Ab

has not been isolated. We screened EBV-transformed peripheral B cells from 12 adult donors for CD4-reactive Ab production followed by functional reconstitution of Fab genes. Three independent IgM Fab clones reactive specifically to CD4 were isolated from a healthy HIV-seronegative adult (∼0.0013% of the peripheral B cells). The germ line combinations for the VH and VL genes were VH3-33/L6, VH3-33/L12, and VH4-4/L12, respectively, accompanied by somatic hypermutations. Genetic analysis revealed a preference for V-gene usage to develop CD4-reactive Ab. Notably, one of the CD4-reactive clones, HO538-213, with an 1×10−8 M dissociation constant (Kd) to recombinant human CD4, limited the replication of R5-tropic and X4-tropic HIV-1 strains at 1–2.

In the following we will discuss the relevance that neurogenesis may play in the aetiology and/or maintenance of two selected diseases, major depression and epilepsy (for an extended review please refer to [62,63]). One of the hallmarks in the aetiology of affective disorders such as major depression is stress, which is among the most powerful negative regulators of hippocampal neurogenesis. Together with the findings that a number of clinically used antidepressants (ADs) such as fluoxetine strongly enhance neurogenesis, the idea was proposed that new neurones may be critically involved

in the disease process of depression and/or represent a potential treatment target [64–66]. This was supported by the clinical observation that a number of ADs require chronic treatment to become effective which may be due to the need for selleck compound AD-induced neurogenesis, which would take several weeks before drug-induced neurones become functionally integrated. An important milestone supporting the relevance of neurogenesis in major depression was a study showing that irradiation-mediated Ibrutinib datasheet inhibition of neurogenesis substantially reduced the ability

of fluoxetine (and other ADs) to affect mood-related behaviour in rodents [67]. However, it became also evident over the last years that not all drugs with AD efficacy require proper neurogenesis to be effective (at least in rodent models of major depression) [68]. Similarly, genetically enhanced neurogenesis by itself does not have mood-manipulating effects under physiological conditions even though see more this genetic, neurogenesis-enhancing approach still needs to be tested in disease models [59]. Mechanistically, the role of new neurones in the context of affective disorders may be twofold. One obvious role of neurones in the context of depressive disease lies in their function in cognitive processes that may amplify/induce disease symptoms. In addition, recent data suggest that new neurones may also directly

serve as a buffer for stress response by having a substantial impact on the hypothalamic–pituitary–adrenal (HPA) axis [69]. Even though it is clear that altered or failing hippocampal neurogenesis is certainly not the only cause of affective disorders, current efforts aim to develop novel strategies to pharmacologically enhance neurogenesis that may help treat depression or ameliorate disease symptoms [66]. In contrast to affective disorders, the key alteration in hippocampal neurogenesis after epileptic seizures is not manifested by a reduction in newborn neurone numbers but rather by an initial increase in newborn neurone numbers followed by aberrant maturation and ectopic migration within the dentate circuitry [70–74].

Thus, the original question posed at the end of the 19th century learn more regarding how the host perceives infection appears to have been solved. While they were the first to be discovered, TLRs are not the only pattern-recognition receptors (PRRs), and subsequent work has uncovered a plethora of recognition molecules. TLRs and C-type lectin PRRs are membrane-bound, found at the cell surface and in endosomes. Many additional PRRs are found in the cytoplasm, including the “retinoic acid inducible gene I-like receptors,” “nucleotide binding domain

leucine rich repeat containing receptors” (NLRs), and several other DNA sensors that signal through a crucial adaptor (STING, stimulator of IFN genes) associated with the ER membrane (reviewed in [[25]]). In fact, STING has recently been shown also to function as a direct sensor of cyclic di-GMP (a conserved signaling molecule restricted to bacteria) [[26]]. In addition, the pioneering work of the late Jürg Tschopp [[27]] highlighted the caspase 1-activating function of the “inflammasome,” formed in the cytosol after ligand-driven oligomerisation

of certain NLRs [[28]]. Once activated, caspase 1 controls maturation of members of the interleukin (IL)-1 family, and IL-1 is known to drive fever, a characteristic ofinflammation (reviewed in [[29]]). Unforeseen, a second paradigm shift (the first being the identified link between innate and adaptive immunity) has appeared on the horizon in recent years. There is now compelling evidence that germline-encoded PRRs not only perceive pathogen-induced inflammation, but beta-catenin inhibitor also “sterile (auto)inflammation” by sensing metabolically altered self-components (reviewed in [[30, 31]]), including modified lipids [[32]] and proteins [[33]].These data have supported Matzinger’s view that “danger” as sensed by the innate immune system comes mainly “from the inside” [[34]]. Autoinflammatory responses have been linked, for example, to type 2 diabetes (see the clinically relevant effects

of IL-1 blockers [[35]]) and to certain aspects of this metabolic syndrome [[36]]. Furthermore, chronic autoinflammation is considered as hallmark Y-27632 mw of age-associated arteriosclerosis [[37]]. A third paradigm shift has arisen more recently. PRRs such as TLRs do not discriminate between commensals and pathogens in the gut microbiota. However, there is increasing evidence that TLR signaling in the intestinal epithelium shapes not only intestinal function (reviewed in [[38]]), but also the induction inflammatory Th17 T cells and that of regulatory T cells (reviewed in [[39]]). Thus, T-cell functions appear to be imprinted not only in the thymus but also in the gut. On the morning of 3rd October 2011, we celebrated the announcement that Ralph Steinmann along with Bruce Beutler and Jules Hoffmann had been awarded the Nobel Prize for Physiology and Medicine.

4b). Hence, even though CD8+ T cells from 8.3-NOD.Il21−/− mice show reduced proliferation to the cognate antigen, their ability to become cytolytic effector

cells upon antigen stimulation was not compromised. Adoptive transfer of polyclonal CD8+ T cells from Il21ra−/− NOD donors, along with IL-21Rα-deficient CD4+ T cells, failed to induce T1D in NOD.Scid recipients [9, 11], suggesting that homeostatic expansion alone is insufficient selleckchem to elicit the pathogenic potential of IL-21-deficient diabetogenic CD8+ T cells. However, the failure of Il21ra−/− to develop T1D could be reversed by the transfer of wild-type DCs [11]. These reports indicated that inefficient activation may underlie the inability of 8.3 T cells to cause disease in 8.3-NOD. Il21−/− mice. Given that IL-21 deficiency did not diminish the ability of 8.3 T cells to develop effector functions upon antigen stimulation (Fig. 4a,b) and to undergo homeostatic expansion (Fig. 3), we investigated whether previous antigen stimulation would enable 8.3 T cells to induce T1D in NOD.Scid mice. To this end, we stimulated IL-21-deficient and control 8.3 CD8+ T cells with the cognate peptide IGRP208–214 for

2 days before adoptive transfer to NOD.Scid recipients. NOD.Scid mice lack both NK T cells and CD4+ T cells, the major producers of IL-21 [15], and hence IL-21 is unlikely to be available to the activated donor cells. As shown in Fig. 4c, IL-21-deficient 8.3 CD8+ T cells stimulated by cognate antigen in vitro induced T1D in all NOD.Scid recipients within 10 days after adoptive transfer, as in the case of wild-type Z-VAD-FMK price donor cells. Even though the proportion of CD8+ T cells in the lymph nodes was reduced substantially in recipients of IL-21-deficient donor cells compared to recipients of wild-type cells (Fig. 4d), both groups of mice showed a similar level of islet infiltration (Fig. 4e) and developed T1D (Fig. 4c). To determine whether IL-21 produced

by donor cells is sufficient for T1D induction, we transferred splenocytes adoptively from diabetic NOD mice to NOD.Scid and NOD.Scid.Il21−/− recipients. As shown in Fig. 4f, both groups of recipient Nintedanib (BIBF 1120) mice developed T1D between 30 and 50 days after cell transfer, suggesting that IL-21 available from donor cells is sufficient for activated diabetogenic cells to induce disease. In addition, antigen-stimulated 8.3 T cells from IL-21-deficient mice caused diabetes in NOD.Scid.Il21−/− mice within 10 days (Fig. 4c). Collectively, the above results indicate that IL-21 is required for efficient activation of diabetogenic CD8+ T cells by antigen, but is dispensable during subsequent stages of islet destruction. Hence, the inability of 8.3-NOD.Il21/− to develop T1D is related most probably to the defective activation of 8.3 T cells by the endogenous autoantigen IGRP. As activation of naive T cells occurs first in draining lymph nodes, we investigated whether diabetogenic CD8+ T cells from 8.

It has already been demonstrated that the degree of bronchial reactivity to histamine or metacholine correlates with asthma severity measured as symptom scores, treatment required

to control symptoms and diurnal variability of lung function parameters [21, 22]. Interestingly, it has been demonstrated that CD14++ CD16+ cells are potent producers of many pro-inflammatory cytokines while stimulated with viral nucleic acids indicating their possible role in regulation of the inflammatory response [9] Surprisingly, however, we have not been able to demonstrate any direct correlation between the number of CD14++ CD16+ cells and any of the conventional click here parameters reflecting intensity of airway inflammation such as FeNO or peripheral blood eosinophilia. Therefore, we cannot provide evidence that CD14++ CD16+ monocytes significantly affect the intensity of allergic inflammation in response to allergen challenge. However, it cannot be excluded that in asthmatic patients, those cells may affect AHR through modulation of inflammatory response to respiratory infections including viral infections. Dysfunction of the airways seen in asthmatic patients depends not only on airway inflammation but also on structural changes in the airways referred to as remodelling. Although airway inflammation leads to development

of bronchial reactivity, in asthmatic patients, successful therapy with inhaled corticosteroids has only selleck chemical mild effect on AHR [23, 24]. Anti-inflammatory effects of corticosteroids in asthma are Carbohydrate associated with dramatic depletion of inflammatory cells, mainly eosinophils and lymphocytes from the airway tissues [24]. However, some structural changes in the airways are resistant to corticosteroid therapy [24]. It has been recently demonstrated that the degree of bronchial responsiveness to histamine but not to metacholine correlates with airway remodelling [25]. It is therefore tempting to speculate that the disequilibrium between individual PBM subsets may

participate in the development of airway remodelling and AHR. The CD16+ monocytes play a role in tissue remodelling and angiogenesis [8, 10, 26]. Analysis of transcriptomes demonstrated that among all PBM subsets, the CD14++ CD16+ cells are characterized by the greatest expression of genes involved in tissue remodelling and angiogenesis such as TGFB1 or CD105 [10]. Moreover, the Th-2 type cytokines such as IL-4 and IL-13, which are abundantly produced in allergic asthmatics, induce differentiation of monocytes into profibrotic and angiogenic macrophages, which in turn play a crucial role in remodelling of the lungs leading to pathological fibrosis [27]. Further insights into the potential role of individual PBM subsets in asthma are provided by analysis of their kinetics after allergen challenge. Decrease in the number of CD14++ CD16+ PBMs after allergen challenge may reflect different chemotactic potential of those subsets.

Taken together, we report here that the absence of LFA-1 promotes more severe EAE with increased demyelination and increased numbers of inflammatory CX-4945 order cells migrating into the CNS. Moreover, we demonstrate that the loss of LFA-1 led to impaired generation of Treg, which in turn explains the observed overshooting autoimmune response

against the MOG antigen. To examine the role of LFA-1 in EAE induction, we used a standard mouse model based on the subcutaneous immunization of C57BL/6 mice with MOG35–55 peptide emulsified in CFA. The experiment was performed with WT (LFA-1+/+), LFA-1-deficient (LFA-1−/−), and heterozygous mice (LFA-1+/−) as an additional control. LFA-1+/− mice express LFA-1 at an intermediate level (data not shown). All experiments were performed with littermates Galunisertib order to exclude any effects of different C57BL/6 substrains. WT mice typically developed first clinical signs of EAE between days 10 and 15 and reached the peak of disease between days 18 and 23. Clinical signs persisted on the peak level for at least 5–7 days before they slowly decreased. Interestingly, LFA-1 KO animals developed dramatically aggravated clinical signs and reached significantly higher clinical scores over the whole observation period (mean cumulative disease score until

day 29: 31.4 versus 14.7, p<0.0001, calculated across three independent experiments with n=28 or n=27 animals per group). A typical experiment is shown in Fig. 1 and Table 1. In addition, the incidence of EAE through day 21 was clearly higher, with 97.5% (±5.6) diseased LFA-1−/− compared with 69.8% (±6.8) LFA-1+/+ animals (incidence +/− SEM, calculated from six independent experiments with n=7–15 animals per group). In terms of clinical signs, LFA-1+/− mice behaved similar to the WT mice, indicating that the intermediate expression of LFA-1 in these mice is sufficient for the biological function. EAE pathology is mainly caused by the infiltration of inflammatory cells into the CNS tissue. This local inflammation subsequently leads to demyelination and axonal

damage. We therefore analyzed the spinal cord IKBKE of diseased mice for typical signs of inflammation and demyelination by histology (Fig. 2). At the peak of the disease, significantly more perivascular infiltrates per spinal cord cross-section were found in LFA-1−/− mice compared with LFA-1+/+ (LFA-1−/−: 4.4±1.0, LFA-1+/+: 1.16±0.28, and p=0.024). Similarly, the extent of demyelination was significantly more prominent in LFA-1−/− (9.31±1.9%), whereas in LFA-1+/+ almost no demyelination was observed (0.76±0.48%; p=0.004). Moreover, in three out of the five LFA-1−/− mice prominent inflammatory infiltrates were detected in cerebellum and/or brain, whereas in the LFA-1+/+ mice only sparse inflammatory infiltrates in the cerebellum and/or brain were found (Fig. 2B).

The most relevant finding of this study is that TLC immunostaining

could potentially identify the presence of aPL in patients with clinical features suggestive of APS not ascertained by traditional tests for aPL, and such identification could have a major impact on the prognosis and therapeutic approach. Moreover, our results suggest the biological activity of these antibodies that are able to trigger a signal transduction see more pathway(s) in endothelial cells with consequent proinflammatory and procoagulant effects in vitro. However, currently testing for TLC immunostaining is not suitable for screening purposes, and larger prospective studies are needed to assess its clinical relevance as a rescue test for patients with suspected APS but persistently negative for conventional find more aPL. This work was supported by grants from Fondazione Umberto di Mario ONLUS, MIUR-PRIN 2007. A patent relating to the content of the manuscript is applying. Fig. S1. Interleukin (IL)-1 receptor-associated kinase (IRAK) phosphorylation assay and nuclear factor (NF)-κB activation by seronegative anti-phospholipid syndrome (SN-APS) immunoglobulin

(Ig)G fraction from three different patients. Eahy926 cells were incubated with SN-APS IgG (200 μg/ml) from three different patients (Table S1, patients 32, 34 and 35, respectively) for 45 min at 37°C and thereafter whole and nuclear extracts were probed with polyclonal rabbit anti-phospho-IRAK (a) or polyclonal rabbit anti-phospho-NF-κB p65 (b), respectively. Bound antibodies were visualized with horseradish peroxidase (HRP)-conjugated check details anti-rabbit IgG and immunoreactivity was assessed

by enhanced chemiluminescence (ECL). As a control for loading, IRAK blots were stripped and reprobed with polyclonal anti-actin antibody (a), phospho-NF-κB p65 blots were stripped and reprobed with polyclonal anti-histone H1 (b). Fig. S2. Tissue factor (TF) release by seronegative anti-phospholipid syndrome (SN-APS) IgG fraction from three different patients. Cells were stimulated with SN-APS immunoglobulin (Ig)G (200 μg/ml) from three different patients (Table S1, patients 32, 34 and 35, respectively) for 4 h at 37°C. After treatment, the supernatants were collected and analysed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results are expressed as mean ± standard deviation from three different experiments. Table S1. Clinical and serological profile of seronegative anti-phospholipid syndrome (SN-APS) patients. “
“The interaction of T cells with antigen-presenting cells is the hallmark of adaptive immunity. In vitro studies have described the formation of an immunological synapse between these cells, and intra-vital imaging has described in great detail the dynamics of these interactions.