An internal standard is used to ensure precision in mass determination. The result is that the Ibis

universal biosensor detection system can identify the amplicons produced by a carefully designed primer set, with a high degree of accuracy that is stated as a percentage in the ‘read out’ data and with a sensitivity that detects all organisms present as >1% of the total microbial population in the sample. The system also detects and identifies fungi and viruses, and detects the presence of the bacterial genes that control resistance to antibiotics. Primer sets can be designed Selleck SP600125 to focus on the pathogens usually seen in a particular medical situation, such as orthopedic infections, so that sensitivity and accuracy can be enhanced in the parts of the bacterial ‘tree of life’ (Fig. 5) in which the majority of the ‘usual suspects’ are located. The time required for DNA extraction is short, except in exceptional cases, and the PCR amplification process is rapid and automated, so that the Ibis system can detect and identify all of the bacteria present in a sample in <6 h, and biofilm cells are detected with the same sensitivity as planktonic cells. We have initiated prospective

double-blinded studies of both suspected infections of total joint prostheses, and of infected nonunions of the tibia/fibula following open trauma, in which we will compare data obtained from cultures with data generated using the Ibis system. Clinical decisions will be based on culture data because the Ibis system is not yet FDA approved, but after the code has been broken, Fludarabine the sensitivity and accuracy of the Ibis system will be compared with that of cultures. In addition, the Ibis data will be considered retrospectively, as a potential basis for clinical decisions, in the light of clinical outcomes and in the light of additional evidence of the presence of bacterial biofilms, such as direct microscopic evidence using FISH probes. If selleck chemical the sensitivity and accuracy of the Ibis system are seen to exceed those

of traditional cultures, we will support their adoption for the diagnosis of bacterial infections in all aspects of orthopedic surgery. “
“Here, we report on the successful programming of dendritic cells (DCs) using selectively applied mixtures of chemokines as a novel protocol for engineering vaccine efficiency. Antigen internalization by DCs is a pivotal step in antigen uptake/presentation for bridging innate and adaptive immunity and in exogenous gene delivery used in vaccine strategies. Contrary to most approaches to improve vaccine efficiency, active enhancement of antigen internalization by DCs as a vaccine strategy has been less studied because DCs naturally down-regulate antigen internalization upon maturation. Whereas chemokines are mainly known as signal proteins that induce leucocyte chemotaxis, very little research has been carried out to identify any additional effects of chemokines on DCs following maturation.

amazonensis parasites. We could not detect CD4+ that were able to produce IL-10 and IFN-γ simultaneously and did not observe any differences in the frequency of IL-10+CD4+T cells, or in CD4+CD25highIL10+ regulatory T cells between LbAg and LaAg stimulation ITF2357 price (data not shown). There are indications that L. amazonensis infection induces IL-10 production by macrophages [51–53] and regulatory B cells [54], which were not evaluated in the present work. These possibilities are currently being investigated, as we are now also looking for IL-10 production by other cell types. As shown in Fig. 2a and b, LbAg induced significantly higher proportions of multifunctional

triple-positive (3+) CD4+T

cells than LaAg, corresponding to 28% of the total Th1 response observed. Forty-four per cent (44%) of the LbAg responding cells were double-positives Antiinfection Compound Library and 21% were single-positives for IFN-γ. Conversely, 68% of the Th1 responses induced by LaAg were composed of single-positive cells and more than half of those were IFN-γ single-positives (covering 32% of the total Th1 response). Only 10% of the Th1 cells induced by LaAg were capable of producing all three cytokines simultaneously (Fig. 2b). As it has been well demonstrated that IFN-γ single-positive cells are short-lived [24,25], and fail to induce protection in murine L. major vaccine-studies [32], it is possible that one of the mechanisms involved in the poor parasite-specific Th1 response observed in DCL patients is the induction of a great number of short-lived IFN-γ single-positive cells. L. amazonensis

could induce a state of functional exhaustion of CD4 Th1 cells, as was shown recently for CD8+T cells in L. mexicana-infected DCL patients [55]. In our system we were able to detect low percentages of Leishmania-specific cytokine-producing CD8+T cells. All of them were IFN-γ single-positives, but no difference could be observed between LaAg and LbAg stimulation (data not shown). L. amazonensis can also cause localized cutaneous leishmaniasis, and DCL patients may display temporary remission of lesions after therapy, when eventually they can produce Carnitine palmitoyltransferase II low levels of IFN-γ after in vitro Leishmania antigen stimulation [18]. It would be most interesting to study the quality of parasite-specific CD4+T cells generated after LaAg and LbAg stimulation in L. amazonensis-infected patients to evaluate a possible correlation between the induction of multifunctional T cells or IFN-γ single-positive T cells, and the development of CL or DCL in L. amazonensis-infected individuals. We also investigated the relative cytokine concentrations produced by all seven Th1 phenotypes induced by LbAg and LaAg by comparing the geometric MFIs.

IL-10R1 expression levels on CD4+ and CD8+ T cells were correlated negatively with the SLE disease activity index (P < 0·01). Additionally, the phosphorylation of STAT-3 was delayed and reduced in PBMCs from LN patients and active SLE patients. Plasma IL-10 levels were significantly higher in LN patients than controls. IL-10R1 expression on CD4+ T cells and signalling in PBMCs were down-regulated in LN patients,

indicating that IL-10 and its receptor may have a special role in LN pathogenesis. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of numerous autoantibodies and damage to multiple organ systems. As seen commonly in autoimmune diseases, genetic and FG-4592 price (or) environmental factors damage

the immune system and result in the development of SLE [1]. Interleukin (IL)-10 is pleiotropic in its abilities to stimulate B lymphocyte proliferation, immunoglobulin secretion, inhibit T helper Doxorubicin purchase type 1 (Th1) responses, promote Th2 responses and to induce the differentiation of regulatory CD4+ T cells (Tr1) [2]. Because of its potential ability for inducing autoantibody production, IL-10 was presumed to play an important role in the pathogenesis of SLE. Indeed, a series of studies have indicated that IL-10 may play a central role in the pathogenesis of SLE. Llorente and co-workers published the first paper describing IL-10 overproduction by peripheral blood mononuclear cells (PBMCs) from SLE patients [3]. Several subsequent studies also confirmed this observation [4–7]. Furthermore, correlation of serum IL-10 levels with disease activity has been demonstrated in almost all related studies [8–10]. However, the exact contribution ever of IL-10 to the pathogenesis of SLE is undefined, and the origin of IL-10 overproduction is unclear. There was also a report showing that IL-10

can down-modulate murine lupus through inhibition of pathogenic Th1 cytokine responses [11]. Additionally, recent studies have identified some types of regulatory B cells, including B10 cells, whose regulatory effects are mediated by IL-10 [12–15], suggesting that IL-10 has a protective effect during lupus progression. These contradictory results suggest that IL-10 signalling has multiple and complex effects on the development of SLE. As the IL-10 receptor (IL-10R) is an indispensable component of the IL-10 signalling pathway and is expressed differentially on immune cells, we hypothesized that IL-10R might be involved in the development of human or animal lupus. Functional IL-10R is a tetrameric complex composed of two ligand-binding alpha chains (IL-10R1) and two accessory-signalling beta chains (IL-10R2). IL-10R1 expression is critical for IL-10-mediated immune regulation [16].

Databases searched: MeSH terms and text words for kidney transplantation were combined with MeSH terms and text words for living donor, and combined with MeSH terms and text words for hypertension. The search was carried out in Medline (1950–July Week 3, 2008). The Cochrane

Renal Group Trials Register was also searched for Acalabrutinib concentration trials not indexed in Medline. Date of searches: 24 July 2008. Assessment of living donors’ BP should consider the long-term cardiovascular risk and the presence of hypertension as a surrogate marker of underlying renal disease. The definition of hypertension and how BP should be measured requires some consideration. There is a well-established relationship between cardiovascular risk and degree of hypertension, however, the threshold for concern has been progressively lowered in more recent years. The definition of ‘hypertension’ as a threshold of measurement has been generally considered to be 140/90 mmHg, however, the most recent Joint National Committee now defines increased cardiovascular risk for individuals previously considered to be in the ‘normal’ range, and define a group of patients as ‘pre-hypertension’ with BP readings 120–140 systolic/80–90 diastolic.1 The implication of this redefinition of risk for these patients previously considered to be in

the normal range has not been evaluated for living donors. The method of BP measurement is an additional variable that needs further consideration. Assessment of live donors should MAPK inhibitor include serial manual BP measurements on at least three separate outpatient visits as a minimum evaluation. The majority of studies evaluating BP measurement in the general population relating measurement to cardiovascular risk and morbidity have relied on manual measurement. The role of ABPM continues to be evaluated and has been shown to correlate with end-organ damage2 and predict cardiovascular risk better than manual BP measurement in some studies.3,4 If elevated manual BP is detected, then it may be worthwhile performing home self-BP measurements or ABPM, since 10–20% of patients with

elevated manual measurements have normal BP by ABPM.5–7 A normal BP on home BP measurements or ABPM is an average of less than 135/85 mmHg. If hypertension is detected evidence of end-organ disease should be excluded by echocardiogram Amino acid and ophthalmology assessment. Patients with evidence of end-organ damage should not be considered as donors, including potential donors with poorly controlled BP or those taking multiple antihypertensives. In addition to detecting patients with ‘white-coat’ hypertension, ABPM may also improve the detection of hypertension. Ozdemir et al. studied renal donors and demonstrated that ABPM was more sensitive at detecting hypertensive patients than manual BP.5 Textor et al. also reported that ABPM is useful in the diagnosis of hypertension in renal donors, particularly the elderly.

Methods for immunoblotting and immunostaining of endogenous LC3 have been described (76). Bafilomycin A1 (an inhibitor of V-ATPase) is also used to inhibit autophagy and to estimate the autophagic flux of LC3-II. As V-ATPase contributes

to the acidification of other organelles, including the Golgi and endosomes, bafilomycin A1 may show multiple off-target effects (92, 93). p62 has ubiquitin-binding and LC3-binding domains, and binds to ubiquitylated protein https://www.selleckchem.com/products/H-89-dihydrochloride.html aggregates to degrade them selectively via autophagy (94–96). When autophagy is impaired, p62 increases in cells and tissues (94, 97). At the same time, ubiquitin-positive aggregates accumulate. Ubiquitin-positive and p62-positive aggregates find more are observed in brains in some neurodegenerative diseases and in other autophagy-defective tissues. Therefore, accumulation of p62 and

ubiquitin-positive proteins suggests the possibility of impairment of autophagy. Atg4B is a cysteine protease which is essential for conversion of proLC3 to LC3-I and for delipidation of LC3-II (Figs 1 and 2) (98). A mutant Atg4BC74A, in which the active site Cys74 is changed to Ala, produces defects in conversion and delipidation (Fig. 2, Atg4BC74A) (99, 100). Because overexpression of the mutant Atg4BC74A results in inhibition of LC3 lipidation, that is, in autophagy, the mutant is employed as a dominant negative mutant. Autophagy is a bulk process of degradation of cytoplasmic components, including organelles. The pathophysiological functions of autophagy are becoming clear; however, our understanding of autophagy machinery, and methods for monitoring autophagy, are somewhat less than perfect. CYTH4 We have reviewed both the “core” Atg complexes essential for autophagosome formation, and assays

of autophagy. Mammalian cells have mammalian-specific Atg proteins and more complicated mechanisms than yeast, probably because mammalian cells utilize autophagic machinery for tissue- and cell-specific functions as well as for self defense mechanisms against intracellular and extracellular stresses. In addition to so called “autophagy” as a non-selective function, the presence of selective autophagy has been reported; mitophagy is a type of autophagy specific for degradation of mitochondria, reticulophagy for the endoplasmic reticulum, ribophagy for ribosomes, piecemeal autophagy for the nucleus, and xenophagy for pathogens. Selective autophagy-specific genes are now being isolated and characterized. For future clinical applications based on autophagy, it will be necessary to screen for compounds which inhibit or activate autophagy.

1 g greater LVMI (95% CI 0.5–1.6).118 However, analysis of the NHANES III data did not show any association between high dietary phosphate intake and mortality in 1105 CKD patients (HR 0.98 per 100 mg/dL increase (95% CI 0.93–1.03)).119

Few clinical trials have looked at lowering dietary phosphate absorption in participants with normal phosphate levels to prevent the complications of CKD-MBD. An experimental study using a rat model of CKD-MBD reported animals with reduced GFR fed a grain-based diet, AP24534 molecular weight compared with standard synthetic casein animal diets, had lower serum phosphate, urinary phosphate excretion and serum levels of FGF-23.120 The same investigators conducted a cross-over trial in nine patients (mean eGFR 32 mL/min) and compared vegetarian and meat diets. They reported decreased urine phosphate excretion, lower serum phosphate and decreased FGF-23 levels with a vegetarian diet

after 1 week.121 This study also highlighted that higher dietary phosphate intake was associated with increased FGF-23. Dietary phosphate counselling for CKD patients can be complex and patients are often confused by the multitude of recommendations. Simplifying the approach by asking them to eat more grains and less meat and less pre-prepared or packaged foods may potentially lead to increased dietary adherence and subsequent improved phosphate homeostasis. One study educating ESKD patients on dialysis to avoid phosphate-containing food additives resulted in modest improvements in hyperphosphataemia.122 However, further dietary studies are required in CKD patients as additives are increasingly being added check details to processed and fast foods and the effect of dietary modifications on serum phosphate levels in early CKD is unclear. Despite the rapidly growing body of literature suggesting phosphate dysregulation is associated with increased morbidity and mortality in CKD, what remains to be established is whether early intervention

to prevent phosphate retention can impact on the development of the adverse clinical outcomes associated with CKD-MBD. To date, there has not been an adequately powered, placebo-controlled, multicentre RCT evaluating Tryptophan synthase the effects of phosphate-lowering therapy on reduction of CVD burden in CKD patients. One of the first questions to help design an RCT addressing phosphate homeostasis in early CKD would be to determine the trigger for intervention or the abnormality that one should aim to correct. Hyperphosphataemia occurs late in CKD, at which point arterial or ventricular function may be impaired, so the approach should probably be to intervene before this occurs. Rising phosphate levels within the normal range maybe both a trigger for intervention and its target, but phosphate levels undergo circadian and dietary variation and fasting levels may also be uninformative, so this approach may not prove valuable.

“
“Microcirculation (2010) 17, 226–236. doi: 10.1111/j.1549-8719.2010.00022.x Tissue blood flow is controlled by a branching network of resistance arteries coupled in series and parallel with one another. To alter organ perfusion

during periods of elevated metabolic demand, the arterial segments comprising these networks must dilate in a coordinated manner. Gap junctions are intercellular see more pores that facilitate arterial coordination by enabling electrical stimuli to conduct among and between endothelial and/or smooth muscle cells. Through this novel perspective, readers will be introduced to the vascular communication field, the process of intercellular conduction, and how key cellular properties influence charge flow. This overview will begin with a brief historical review

and then introduce two differing theories on how electrical phenomena moves among and between vascular cells. The basis of the “syncytium” and “differential” hypothesis will be critically discussed within a framework of biophysical and experimental observations. This foundational understanding will be used to extend our mechanistic insight of: (i) “local” and “global” blood flow control; and (ii) debilitating disorders such as arterial vasospasm. “
“Vascular smooth muscle contraction and relaxation play a preponderant role on the active (acute) and structural (long-term) control of vascular diameter. This editorial overview summarizes and highlights the opinions expressed in seven reviews contained in this special topic issue of Microcirculation. Erlotinib The reviews address diverse aspects of the mechanisms that influence cell adhesion, calcium homeostasis, and cytoskeletal

remodeling, and how these mechanisms affect vascular structure and function at different levels of the circulation. “
“Please cite this paper as: Bachmeier, Beaulieu-Abdelahad, Mullan, and Paris (2011). Epitope-Dependent Effects of Beta-Amyloid Antibodies on Beta-Amyloid Clearance in an In Vitro Model of the Blood–Brain Barrier. Microcirculation 18(5), 373–379. Objective:  To investigate the role of RAGE in the epitope-dependent effects of Aβ antibodies Farnesyltransferase used as a peripheral sink therapy in AD. Methods:  An in vitro model of the BBB was used to examine the effect of various Aβ antibodies or Aβ peptide fragments on Aβ exchange across the BBB. Results:  An N-terminal Aβ antibody significantly enhanced the basolateral-to-apical transcytosis of fluorescein-Aβ(1–42) across the BBB model (41%), while no effect was apparent with a C-terminal Aβ antibody. Interestingly, modulation of RAGE in the presence of a C-terminal Aβ antibody resulted in a 65% increase in Aβ clearance across the BBB model, suggesting the C-terminal antibody–Aβ complex is susceptible to RAGE transport.

Seven L. (V.) braziliensis isolates from patients with different clinical forms of leishmaniasis were expanded in interferon-γ knockout mice to obtain amastigotes and in culture to get promastigotes. The parasites

were used to stimulate PBMCs from healthy donors, and cytokine production was evaluated by ELISA or qPCR. Amastigotes and promastigotes induced IL-10 production in PBMCs; however, only amastigotes induced IL-1β, selleck chemicals IL-6 and TGF-β. These data demonstrate for the first time that L. (V.) braziliensis amastigotes directly stimulate production of a unique pattern of cytokines that could contribute to the generation of Th17. “
“Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs most frequently when human platelet antigen (HPA)-1a-positive fetal platelets are destroyed by maternal HPA-1a immunoglobulin (Ig)G antibodies. Pregnancies at risk are treated by administration of high-dose intravenous Ig (IVIG) to women, but this is expensive and often not well tolerated. Peptide immunotherapy may be effective for ameliorating

some allergic and autoimmune diseases. The HPA-1a/1b polymorphism Selleckchem BYL719 is Leu/Pro33 on β3 integrin (CD61), and the anti-HPA-1a response is restricted to HPA-1b1b and HLA-DRB3*0101-positive pregnant women with an HPA-1a-positive fetus. We investigated whether or not HPA-1a antigen-specific peptides that formed the T cell epitope could reduce IgG

anti-HPA-1a responses, using a mouse model we had developed previously. Peripheral blood mononuclear cells (PBMC) in blood donations from HPA-1a-immunized women were injected intraperitoneally (i.p.) into severe combined immunodeficient (SCID) mice with peptides and HPA-1a-positive platelets. PDK4 Human anti-HPA-1a in murine plasma was quantitated at intervals up to 15 weeks. HPA-1a-specific T cells in PBMC were identified by proliferation assays. Using PBMC of three donors who had little T cell reactivity to HPA-1a peptides in vitro, stimulation of anti-HPA-1a responses by these peptides occurred in vivo. However, with a second donation from one of these women which, uniquely, had high HPA-1a-specific T cell proliferation in vitro, marked suppression of the anti-HPA-1a response by HPA-1a peptides occurred in vivo. HPA-1a peptide immunotherapy in this model depended upon reactivation of HPA-1a T cell responses in the donor. For FNAIT, we suggest that administration of antigen-specific peptides to pregnant women might cause either enhancement or reduction of pathogenic antibodies. “
“The altered expression of transcription factors in hematopoietic stem cells and their subsequent lineages can alter the development of lymphoid and myeloid lineages. The role of the transcriptional repressor Snai3 protein in the derivation of cells of the hemato-poietic system was investigated.

It is known that ROS causes mitochondrial damage and plays an important role for the death of activated T cells 27. TSC1KO T cells display increased ROS production, but decreased mitochondrial content, number, and membrane potential. Since the ROS scavenger NAC can reduce the death of TSC1KO T cells and can increase mitochondrial membrane potential, it suggests that

TSC1 may promote T-cell survival mainly through the inhibition DAPT concentration of ROS production to maintain mitochondrial integrity. Of note, CD28 mediated co-stimulation, but not rapamycin treatment, can reduce TSC1KO T-cell death correlated with reduced ROS production and increased mitochondrial potential, but without obvious increase of Akt activity. Thus, TSC1 may inhibit ROS production in T cells and promote T-cell survival through mTOR-independent mechanisms. Further studies are needed to determine the mechanisms by which TSC1 regulates ROS production and mitochondrial homeostasis. The TSC1flox/flox and CD4-Cre transgenic mice were

purchased from Jackson Laboratory and Taconic Farm, respectively 38, 39. All experiments were performed in accordance with protocols approved by the Duke University Institutional Animal Care and Use Committee. Single-cell suspension of thymocytes, splenocytes, and LN cells in IMDM medium supplemented with 10% FBS, penicillin/streptomycin, and 2-mercaptoethanol (IMDM-10) were made according to standard protocols. Purification of T cells was achieved using either the Mouse T Cell Enrichement Kit (STEMCELL Histone Methyltransferase inhibitor Technologies) or the LD depletion columns (Miltenyi Biotech) and purities of ≥90% were achieved. Thymocytes, splenocytes, and purified T cells (5–20×106

cells/mL in PBS) were left PD184352 (CI-1040) un-stimulated or stimulated with 5 μg/mL of anti-CD3ε (500A2; BD Pharmingen) for different times. Cells were lysed in 1% Nonidet P-40 Lysis solution (1% Nonidet-40, 150 mM NaCl, and 50 mM Tris, pH 7.4) with freshly added protease and phosphatase inhibitors. Proteins were resolved by SDS-PAGE and were transferred to a Trans-Blot Nitrocellulose membrane (Bio-Rad Laboratories). The blots were probed with specified antibodies and detected by ECL. Antibodies for TSC1 (♯4906), TSC2 (♯3612), p-Foxo1 (♯9461S), p-ERK1/2 (♯91015), p-p70 S6K (♯9204S), p70 S6K (♯9202), p-4EBP1 (♯2855S), 4EBP1 (♯9644), Cleaved Caspase-3 (♯9661), Cleaved Caspase-9 (♯9509), p-Akt T308 (♯9275S), p-Akt S473 (♯9271S), Puma (♯4976), Bid (♯2003), Bax (♯2772), Bim (♯4582), Bcl-xL (♯2762), Mcl-1 (♯4572), Akt (♯2938), Foxo1a (♯94545), S6K1(♯9202) were purchased from Cell Signaling Technology. Bcl-2 (♯554087) antibody was purchased from BD. Noxa (♯2437) was purchased from ProSci Inc. Anti-β-actin antibody was from Sigma-Aldrich (A1978). Cells were stained with fluorescence-conjugated antibodies specific for CD4, CD8, CD25, CD44, and CD69 (eBioscience and BioLegend) at 4°C for 30 min. Dying cells were identified using 7AAD, annexin V, or the Violet Live/Dead cell kit (Invitrogen).

A number of studies suggested that Treg exert their suppressive function on effector T cells indirectly by modifying the function of antigen-presenting

dendritic cells. Interestingly, a recent in vitro study showed that LFA-1 is important for the formation of dendritic cell/Treg aggregates, because LFA-1−/− Treg were no longer able to inhibit the maturation of cocultured dendritic cells 20. Similar effects were also observed in a mixed human/mouse suppression system 21. We AZD4547 in vivo show here that LFA-1 deficiency results in a reduced Treg/effector cell ratio in the inflamed CNS. The reduction in Treg was already established in the spleen and thymi of unimmunized LFA-1−/− mice. Hence, besides a possible functional impairment of DZNeP cost Treg lacking LFA-1, these results indicate a more fundamental role for LFA-1 in generation of FoxP3+ Treg in the thymus. ICAM-1, a ligand of LFA-1, is expressed on thymic stromal cells 22. Therefore, LFA-1 potentially increases the

physical contact between thymocytes and stromal cells, resulting in enhanced T-cell receptor triggering. Increased T-cell receptor signaling during thymocyte selection favors the generation of naturally occurring Treg 23, which would explain the contribution of LFA-1 to the generation of naturally occurring Treg. So far, LFA-1 has been mainly recognized as a molecule regulating the migration of lymphocytes. Generally, the migration of LFA-1-deficient T cells to the peripheral lymph nodes is impaired, resulting in significantly smaller lymph nodes 10, 14. However, upon immunization with MOG-peptide, we observed that these differences in cellularity in lymph nodes between WT and LFA-1 KO mice are more or less levelled out (data not shown). In the context of EAE and transendothelial migration, Laschinger et al. 11 demonstrated that encephalitogenic Galeterone T cells do not use LFA-1 for the initial adhesion to the endothelium of the blood/brain barrier. Instead, LFA-1 was involved in the later phases of migration into the CNS parenchyma. However, it should be noted that these results were obtained for the healthy spinal cord and that the role of LFA-1 for migration

could be different during later stages of an EAE disease, in which other integrin interactions may compensate for the lack of LFA-1. In our study, we did not directly address the question of lymphocyte migration via the blood/brain barrier. However, the observation that the frequency of MOG reactive CD4+ T cells in LFA-1−/− mice is already higher outside the CNS suggests an impaired suppression of effector T cells by Treg rather than an altered migration as cause for the higher ratio of effector versus Treg in the inflamed CNS in LFA-1−/−. Overall, the exacerbated EAE in the absence of LFA-1 seems to be due to the impaired suppression of autoantigen-specific effector T cells by Treg, which in LFA-1−/− mice show a more extensive expansion in secondary lymphoid organs upon immunization with the MOG-peptide.