Whether this phenomenon Dinaciclib contributes to the enhancement or regulation of allergy is still unclear, since contrasting roles for IL-17 have been described [[54-57]]. The role of IL-17+ γδ T lymphocytes (and of IL-17) in infection, tumor immunity, and autoimmunity has been reported, and it is still controversial [[50, 58-63]]. A clear involvement of IL-17+ γδ T lymphocytes in autoimmunity has been evidenced in experimental arthritis and autoimmune encephalomyelitis, in which these cells have been shown to amplify CD4+ Th17 cell responses, to suppress Foxp3+ Treg cells, and to contribute to the development of the response [[48, 62-64]].

In regard to the participation of IL-17+ γδ T lymphocytes in airway inflammation, it has been recently demonstrated that those cells downmodulate central features of an allergic reaction, including Th2 response and lung eosinophilia [[65]]. Although these regulatory lymphocytes have been shown to express Vγ4 TCR chain, we observed that, in the model of allergic pleural inflammation, Vγ4 T lymphocyte migration was not affected by CCL25 neutralization (not shown). It is noteworthy click here that, in this experimental model, CCL25 neutralization also failed to alter the accumulation of mononuclear cells, T lymphocytes,

and eosinophil in the allergic site, which are major cells that orchestrate the allergic response. Increased levels of CCL25 in synovial fluid from arthritis patients have been reported [[13]]; however whether CCR9/CCL25 play a role in autoimmune and infectious diseases by mediating IL-17+/CCR6+ γδ T lymphocytes is yet to be addressed. Our results reveal a particular in vivo migration pathway for IL-17+ γδ T lymphocytes, which requires CCL25/CCR9 axis and is mediated by α4β7 integrin. Endonuclease Here, we provide evidence that CCL25 plays a pivotal role for IL-17+ γδ T-cell trafficking in allergic response; however, the relevance of this chemokine in Th17-mediated immune responses is yet to be defined. C57BL/6 (18–20 g) provided by Oswaldo Cruz Foundation breeding

unit (Rio de Janeiro, Brazil) were used. All experimental procedures were performed according to The Committee on Ethical Use of Laboratory Animals of Oswaldo Cruz Foundation (Fiocruz, Brazil). Animals received an i.pl. injection of mAb anti-CCL25 (89818; 10 μg/cavity; R&D Systems [Minneapolis, MN, USA]) or an intravenous (i.v.) injection of mAb anti-α4β7 integrin (DATK32; 100 μg/mouse; BD Pharmingen), 1 h before antigenic challenge. Fourteen days after active immunization (50 μg OVA/5 mg aluminum hydroxide, subcutaneously [s.c].), mice were challenged by an i.pl. injection of OVA (12.5 μg/cavity; grade V, Sigma-Aldrich) or rmCCL25 (200 ng/cavity; R&D Systems). Sensitized mice challenged with saline vehicle were used as a negative control group. At specific time points after stimulus, pleural leukocytes were recovered and counted.

However, strong CD8+ T-cell recall responses have also been demonstrated to cause undesired and sometimes DAPT nmr lethal immunopathology in certain circumstances [[9, 10, 16, 31]]. Therefore, rational vaccine design needs to take into account the delicate balance between robust immunity

and lethal CD8+ T-cell-mediated immunopathology. Following LCMV-Arm infection, wild-type mice mount vigorous antiviral CD8+ T-cell responses and clear the virus in a perforin-dependent manner [[40]]. PKO mice fail to clear LCMV-Arm and develop chronic infections [[14]]. Moreover, the requirement for perforin-mediated cytolysis in resistance to primary infection with LCMV is well documented [[41]] and PKO mice are models for FHL [[16-19]], a uniformly fatal disease associated with viral infection in human with mutations in perforin gene [[20, 23-25, 42]]. Thus, perforin Selleckchem Inhibitor Library deficiency represents an immunocompromised state in which defective antiviral CD8+ T-cell response results

in the establishment of chronic infection [[16]]. Previous work in our laboratory demonstrated that vaccination to generate memory CD8+ T cells can overcome perforin deficiency and provide enhanced resistance against intracellular infection with LM [[27, 30]]. In contrast, vaccination of BALB/c-PKO mice results in accelerated mortality following LCMV infection [[16]]. In this case, vaccination of PKO hosts converts a nonlethal persistent infection into a rapidly fatal disease mediated by CD8+ T cells. To understand why vaccination leads to mortality in the absence of perforin, we analyzed multiple parameters that could potentially contribute to the drastic, and ultimately fatal response Mannose-binding protein-associated serine protease observed. We have shown that vaccination-induced mortality is mediated by massive expansion of

NP118-specific memory CD8+ T cells and the associated aberrant cytokine production in PKO mice. Different vaccine strategies did not alter the outcome as long as the number of NP118-specific memory CD8+ T cells exceeds a certain threshold number. In our adoptive transfer experiments (Fig. 3), we observed that the majority of PKO mice succumbed to LCMV infection if they received at least 8 × 104 NP118-specific CD8+ T cells. Assuming 10% “take” of the transferred number, this result indicated that as few as 8000 NP118-specific CD8+ T cells in the spleen at the time of LCMV infection would be sufficient to cause mortality in these PKO mice. Although we did not observe any mortality in mice that received 8 × 103 NP118-specific memory CD8+ T cells (i.e. 800 memory cells in the spleen, assuming 10% take), we documented severe morbidity as significant weight loss in these mice following LCMV infection (Fig. 3C). Thus, even a small number of NP118-specific memory CD8+ T cells is sufficient to cause immunopathology after LCMV infection of PKO mice.

Thus, it is important to keep in mind that a certain level of DC maturity may be important for the generation of Tregs capable of inhibiting autoimmune disease [25]. The development of conventional lymphoid organ DCs in mice has been clarified recently [26]. The macrophage and DC precursor gives rise to the common DC precursor (the source of both conventional and plasmacytoid DCs). The next developmental stage for the conventional lymphoid organ DC is the pre-DC. The pre-DCs expand in the bone marrow and differentiate to conventional DCs within the spleen and click here lymph nodes, where they proliferate in response to Flt3L [27]. A number of DC subsets have been

described phenotypically in both mice and humans [28]. Some of these are known to be functionally specialized [29]. For example, in mice, the DC subset expressing CD8 and DEC-205 is specialized for capture of dying cells [30] and cross-presentation of antigens on class I major histocompatibility

complex (MHC) molecules [31–33], while CD8-DCIR2+ DCs are proficient at presentation of peptides on class II MHC [32]. In addition to their well-established role in central tolerance [34], DCs employ a variety of diverse strategies and pathways to maintain T cell tolerance in the periphery (Fig. 1). Apart from induction of deletional tolerance of peripheral T cells [20,35], DCs in the steady state can also render them anergized [20] as a result of antigen recognition without sufficient co-stimulation [36]. T cell co-inhibitory molecules that transduce selleck screening library negative signals, such as cytotoxic T lymphocyte antigen-4 (CTLA-4) [37] or programmed death-1 (PD-1) [38,39],

also participate in these processes. For example, steady-state DCs utilize both the PD-1 and CTLA-4 Idoxuridine pathways to induce peripheral tolerance of CD8+ T cells [40]. In addition to induction of deletion or anergy, DCs can induce increased expression of CD5 on activated T cells that leads to hyporesponsiveness, at least in the setting of the induced autoimmune disease, experimental acute encephalomyelitis [41]. Expression of Fas on antigen-presenting cells is also important for the maintenance of peripheral tolerance and the avoidance of autoimmunity [42], while the production of indoleamine 2,3-dioxygenase (IDO) by DCs is involved in peripheral tolerance in certain specialized settings [43,44]. Finally, DCs are involved in the in vivo expansion of thymic-derived natural CD4+CD25+ Tregs[45] as well as the induction of adaptive forkhead box P3 (FoxP3+) Tregs[45–48] and CD8+ Tregs[49], and interleukin (IL)-7 produced by immature DCs appears to function as a CD4+CD25+ Treg survival factor [50]. Multiple lines of investigation indicate that priming of pathogenic beta cell-specific T cells occurs in the pancreatic lymph nodes. For example, adoptive transfer of 5,6-carboxy-succinimidyl-fluorescein-ester (CFSE)-labelled transgenic CD4+ BDC2.

Mechanisms by which signals from outside the CNS can alter microglial activation are also discussed. The authors describe animal studies indicating Stem Cell Compound Library that age-related changes in microglia cause impairment of neurogenesis and neuronal plasticity together with associated

cognitive deficits. Importantly, when considering extrapolation towards therapy in humans, reversing the neuroinflammation has functional benefits. The information in this review provides an important basis with which to understand how the ageing brain reacts to superimposed neurodegenerative pathology, the effects of systemic inflammation and reactions to brain injury. Since the observations of Corsellis and Bruton in the 1970s documenting neurodegenerative pathology in the brains of boxers suffering from dementia pugilistica, there have been intriguing hints linking traumatic brain

injury and subsequent long-term progressive neurodegeneration. There has recently been a resurgence of interest in this field, which has come in particular from North America, concerning repeated head injuries sustained as a result of sporting activities such as ice hockey and football and their associated long-term effects (chronic traumatic encephalopathy). The review by PLX4032 Colin Smith of the effects of traumatic brain injury, both single and repetitive, on microglial activation and neurodegeneration, is therefore particularly timely. He develops the argument that microglial activation as a response to

injury in the short tem is beneficial, removing cell debris and promoting tissue repair. However, if the activated state of microglia is not subsequently down-regulated, it may become self-perpetuating and lead to chronic neurodegeneration associated with accumulation of neurodegeneration-related proteins such as tau, amyloid-β and TDP-43. Stephen Gentleman considers in detail the relationship between accumulation of different neurodegeneration-associated proteins in the CNS and microglial activation: are they simply reacting to the pathology, Baf-A1 purchase are they instrumental in the pathogenesis of neurodegenerative disease, or both? He compares and contrasts our current knowledge of the contribution of microglia in a disorder with extracellular aggregation of protein (AD) and those with intracellular protein aggregations (amyotrophic lateral sclerosis and Parkinson’s disease). Clive Holmes considers the evidence that inflammation in the CNS cannot be considered in isolation from inflammation occurring elsewhere in the body (that is, systemic or peripheral inflammation). Information from clinical and preclinical studies shows that peripheral inflammation due to infection or other causes including rheumatoid arthritis, diabetes and atherosclerosis, has an effect on cognitive function both acutely and in the long term.

[13, 14] Similar studies in patients with haematological malignancies and HSCT[15-18] or solid organ transplantation[19, 20] with invasive aspergillosis have demonstrated several prognostic risk factors of mortality, which may assist in the development of treatment intensity algorithms and clinical trials. In our univariate analysis, 12 such variables were found to be significantly different between 4-week survivors and non-survivors; male sex, total bilirubin, thrombocytopenia, LDH, creatinine clearance, acidosis, GvHD, active malignancy,

severe neutropenia, lymphocytopenia, monocytopenia and voriconazole breakthrough infection. Nevertheless, multivariate analysis accounting for severity of underlying disease revealed only baseline severe lymphocytopenia and a high LDH serum level (>655 mg dl−1) GSK1120212 order as independent predictors of early death. Selleck JAK inhibitor Consequently, we identified two different prognostic groups using these variables: patients with a 28-day crude mortality rate of <15% (score ≤22) and

patients with a mortality rate of 75% (score >22). The outcome of mucormycosis depends on several factors, including the site of infection, the immune status of the host and the use of surgery or other adjunctive treatments.[21, 22] Chamilos et al. [7] reported that the initiation of polyene therapy within 5 days after diagnosis of mucormycosis was associated with improvement in survival, compared with initiation of polyene therapy at ≥6 days after diagnosis (83% vs. 49% survival). In the same study,

active malignancy (P = 0.003) and monocytopenia (P = 0.01) at the time of diagnosis of infection were also independently associated with a poor outcome, whereas salvage posaconazole-based therapy (P = 0.01) and neutrophil recovery (P = 0.009) were predictive of a favourable outcome.[7] However, this analysis included patients prior to 2000 when diagnosis and treatment outcomes were considerably worse than the NADPH-cytochrome-c2 reductase current era. Likewise, previous investigators have emphasised the important role of early neutrophil recovery and treatment with high-dose amphotericin B.[23-25] Of interest, a recent prospective study on 20 patients with mucormycosis (with pulmonary and non-pulmonary sites of infection) showed that active malignancy (P = 0.03), neutropenia (P = 0.03) and iron overload (P = 0.03) were significantly associated with 90-day mortality in univariate analysis, whereas no association was found with amphotericin B dose or the use of other antifungal therapy (i.e. echinocandin and posaconazole).[8] Nevertheless, in the current study, only lymphocytopenia and high LDH levels, which probably reflects activity of the underlying malignant disease, were significant risk factors for poor outcome when analysis was adjusted for underlying severity of illness (APACHE II).

20 Moreover the histamine receptor expression pattern is similar to what is known for other DC subtypes, such as MoDC.15 The newly described H4R is of particular interest in inflammatory

skin diseases21 and immunomodulatory effects on DC were already identified so we decided to study this receptor in more detail. By flow cytometry we could show that slanDC express the H4R on the protein level and that the expression level does not change during culture of the cells. We did not observe differences in the basal H4R expression level in diseases like AD and psoriasis, but the Th1-associated cytokine IFN-γ led to an up-regulation of H4R expression of slanDC isolated from patients with AD, whereas in healthy and psoriatic cells no difference was observed. The Th2-associated cytokine IL-13 and the toll-like receptor Bafilomycin A1 clinical trial ligand poly selleckchem I:C could not significantly modulate the expression of H4R in any of the studied groups. The increase of H4R expression upon IFN-γ stimulation was also described

for inflammatory dendritic epidermal cells,16 a subset of DC only present in the inflamed skin of AD patients.22 In chronic lesions of AD, predominantly IFN-γ and other Th1 cytokines are present, therefore it is likely that slanDC up-regulate the expression of the H4R during and after the infiltration to these tissues. Interestingly we did not find up-regulation of the H4R on slanDC derived from psoriasis patients, although this disease is also

Th1-mediated. Possible explanations for this observation could be disease-dependent differences in IFN-γ-mediated signalling or variations in the expression density of IFN-γ receptors. It has been shown for example that atopic diseases are associated with genetic polymorphisms in the IFN-γ receptor 1 gene leading to higher transcription of this receptor.23 To study the functional effects of histamine on slanDC, we stimulated PBMC as well as isolated slanDC with histamine and H4R agonists. After histamine stimulation we observed impaired intracellular production and release into the supernatant (-)-p-Bromotetramisole Oxalate of the pro-inflammatory cytokines TNF-α and IL-12 in response to slanDC activation by the toll-like receptor agonist LPS. Although the down-regulation of TNF-α was solely mediated via the H4R, we observed a dual H2R and H4R mediated effect for IL-12, which is in accordance with previous findings on MoDC.15 These observations strongly suggest that histamine impairs the pro-inflammatory capacity of slanDC, because the key cytokines of early immune responses are no longer produced in high amounts. Interleukin-12 is an important activator of natural killer cells and induces the differentiation of CD4+ T cells into Th1 cells. TNF-α belongs to the family of acute-phase proteins and is known to induce inflammation and apoptosis, to lead to vasodilatation and increased vascular permeability and to be a potent activator of endothelial cells.

Many studies have documented the mechanisms of homing of HSCs into the BM and recirculation of these BM HSCs into the blood. CXCR4+ HSCs are attracted to the BM by the SDF-1 chemokine produced by BM stromal cells. Binding of SDF1 to CXCR4 activates the very-late activation antigen type 4 (VLA-4) PS-341 chemical structure integrin of HSCs which can adhere to endothelial VCAM1+ cells.6 HSCs are recruited to SDF-1+ stromal cells which are adjacent to endothelial cells. Upon injury, HSCs migrate to the closest osteoblasts which produce various growth factors, such as granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6).7 More recently,

BM stromal cells have been shown to express β3 adrenergic receptors.8 Norepinephrine production learn more by the sympathetic nervous system controls expression of homing molecules by stromal cells. It is noteworthy that a circadian fluctuation of norepinephrine production results in circadian release of a minor population of HSCs into the PB. In mice, these circulating HSCs have been shown to play an important role in innate immune surveillance.9 Accordingly, circulating HSCs home to tissues where they may reside for 36 hr before returning to the PB through the lymphatic system. In the case of infection,

Toll-like receptor-mediated activation of HSCs results in down-regulation of the sphingosine phosphate receptor and in situ differentiation of HSCs into innate immune cells: tissue-resident Adenosine triphosphate myeloid cells, preferentially dendritic cells.10 This tightly controlled homing of HSCs into the BM and recirculation into the

PB may explain why human CD34+ HSCs injected into the PB can rapidly home to and engraft the BM and vice versa. At the same time, it may also explain why HSCs can be mobilized into the PB after CXCR4 antagonist or G-CSF injection.11 The effect of G-CSF is mainly attributable to activation of BM myeloid cells to produce proteases that cleave SDF-1 and adhesion molecules.8 Given the similarity of the PC and HSC BM niches in mice, it is tempting to postulate that similar mechanisms exist for the homing of PCs into the BM and eventually for their recirculation from the BM to the PB. Regarding PC homing, it has been shown that deletion of CXCR4 abrogates homing of murine PCs into the murine BM, similarly to HSCs.12 Regarding the exit of BM PCs into the PB, 2 CD19+ CD20− CD38++ PCs/mm3 have been reported in human adults in steady-state conditions.13,14 The origin of circulating PCs remains undetermined but they may be either newly generated PCs in the lymph node or long-lived tissue PCs. After vaccination with tetanus toxin (TT), there is a 4–5-fold increase in the number of circulating PCs, a significant fraction of which do not secrete anti-TT Abs.15 This suggests that newly generated PCs can displace old PCs from their niche and induce them to recirculate.

Approaches to enhance antimicrobial penetration in biofilms have been evaluated by different research groups. Alipour et al. (2009) reported that co-administration of DNase and alginate lyase significantly enhance activity of certain aminoglycosides in reducing biofilm find more growth and cystic fibrosis sputum bacterial counts of P. aeruginosa (Alipour et al., 2009). Lipopeptide biosurfactant produced by Bacillus licheniformis was shown to significantly enhance the efficacy of antibiotics in killing E. coli biofilms (Rivardo et al., 2011). Micelle-encapsulated antibiotics and antibiotic-encapsulated

biodegradable polymeric nanoparticles are also reported to efficiently kill biofilm cells (Jones, 2005; Cheow et al., 2010). Efflux pump systems are involved in biofilm formation and antimicrobial resistance (Pamp et al., 2008; Zhang & Mah, 2008). Inactivation of efflux systems by efflux pump inhibitors was reported to abolish bacterial biofilm formation or enhance antimicrobial activity against biofilms (Kvist et al., 2008; Liu et al., 2010). In recent years, phages are suggested as alternatives to antibiotics for the treatment of biofilms. Phages are inexpensive and specific against a host or host range, and will not affect the normal microflora of the environment where they are applied. A T7-like lytic phage against P. aeruginosa isolated from Pavana river water has been shown to prevent

and disperse biofilms of P. aeruginosa (Ahiwale et al., 2011). Carson et al. (2010) reported that lytic bacteriophages could eradicate www.selleckchem.com/GSK-3.html established

biofilms of Proteus mirabilis and E. coli, and impregnation of hydrogel-coated until catheter sections with these lytic bacteriophages could prevent biofilm formation on catheter biomaterials (Carson et al., 2010). Some phages also possess polysaccharide-degrading enzymes that can rapidly destroy the integrity of biofilms (Suthereland et al., 2004). A P. aeruginosa-specific phage was isolated and shown to produce alginase to depolymerize the alginate capsule from the mucoid cystic fibrosis isolates of P. aeruginosa (Glonti et al., 2010). This alginase might accelerate phagocytic uptake of bacteria and perturb bacterial biofilms of patients with cystic fibrosis. An engineered bacteriophage which expresses a biofilm-degrading enzyme during infection was reported to simultaneously attack the biofilm cells and the EPS matrix (Lu & Collins, 2007). A cell-wall-degrading enzyme SAL-2 from a new podoviridae S. aureus bacteriophage (SAP-2) was cloned and expressed by Son et al. (2010). The SAL-2 enzyme has specific lytic activity against S. aureus with a minimum inhibitory concentration of about 1 μg mL−1 and can efficiently remove S. aureus biofilms (Son et al., 2010). Phages are also reported to improve the conventional antimicrobial treatment to biofilm related infections. Verma et al.

Incidentally, Fujii et al. 8 reported a phenomenon describing NKT cell turnover, a decrease in the NKT cell population on day 1 after α-GalCer administration later found to be due to TCR down-regulation, after administration of free α-GalCer that was “less rapid and severe” when DCs pulsed with α-GalCer were administered. Antigen-specific cellular this website immune responses were measured after each dose of the α-GalCer adjuvant and OVA antigen mixture, similar to our previously reported studies with a different antigen 7. Both these studies demonstrate that multiple doses of α-GalCer, administered by the intranasal route, are necessary to induce

efficient antigen-specific cellular immune responses, regardless of the mouse strain used. In addition to the antigen-specific cellular immune responses, effectiveness of α-GalCer as an adjuvant after intranasal immunization to induce humoral immune responses, in terms of antigen-specific IgA and IgG responses has been described in the literature

24 and also observed in other unrelated studies in our laboratory (data not shown). Thus, our studies provide mechanistic support for mucosal delivery of α-GalCer adjuvant as an attractive strategy for vaccination regimens. It is also important to note potential inflammatory effects from the intranasal administration of α-GalCer. Different mouse model studies revealed that intranasal administration of α-GalCer can induce airway infiltration of a combination of eosiniphils, neutrophils, see more and/or monocytes 25, 26. Preliminary studies in our lab showed increase in the percentages of eosinophils but not neutrophils or monocytes (data not shown). However, clinical trials performed by Kunii et al. 4 showed that administration of α-GalCer by a nasal sub-mucosal route was safe. Overall, this investigation has shown that α-GalCer can be administered by the intranasal route for primary and booster immunizations to induce cellular immune responses to co-administered antigens, without inducing NKT cell anergy. This is in striking contrast to α-GalCer administration

by the intravenous route, in which a single dose leads to NKT cell anergy and a reduction in the ability of the adjuvant to boost adaptive immune responses to co-administered antigen. Thus, Progesterone our data support the intranasal route of immunization as an attractive route for immunization especially because the ability to deliver multiple doses of the vaccine is essential for most therapeutic applications against infectious diseases and cancer. Female C57Bl/6 mice aged 6–10 wk were purchased from the National Cancer Institute. All procedures on the animals were carried out in accordance with institutionally approved protocols. The animals were housed in microisolator cages and provided with sterile food and water. The animal facility is fully accredited by the Association for Assessment and Accreditation of Laboratory Animals Care International.

Meier-Kriesche et al. showed that both abnormally low and abnormally high BMI are risk factors for decreased patient and graft survival, independent of most of the known risk factors.3 On the other hand, other studies failed to show the impact of obesity on renal Selleck Torin 1 graft survival.4,5 A BMI of 30 kg/m2 has been used as a cut-off point for obesity in white subjects. According to the contemporary American Society of Transplantation guidelines, a goal weight BMI

of less than 30 kg/m2 is desirable prior to renal transplantation.6 However, there is now international consensus that this cut-off point is too high for the Asian general population in terms of cardiovascular consequences.7 In 2000, the World Health Organization Western Pacific Regional Office proposed a modified BMI cut-off value of 23 kg/m2 to define overweight and 25 kg/m2 to define obesity in Asian populations (Table 1).8 These cut-off values are also validated in our Chinese population.9 The data concerning the impact of BMI on graft outcome in Asian renal transplant recipients is scarce. Chow et al. showed that baseline BMI of 25 kg/m2 or more conferred a significantly higher risk of graft loss and doubling of serum creatinine.10 However, there is a lack of data showing whether overweight

(BMI ≥23 kg/m2) also results Neratinib order in an increased risk of mortality and morbidity in Asian renal transplant recipients. The aim of this study is to identify the relationships between different BMI cut-off values at time of transplantation and graft outcome in Asian renal transplant recipients. We will also examine different factors which can

predict graft survival. This was a single-centre retrospective cohort study which included all Chinese patients who received solitary living-related or deceased kidney transplantation from 1 July 1997 to 31 July 2005 in Queen Elizabeth Hospital, Hong Kong. Initially we analyzed two separate cohorts this website of patients based on the BMI at the time of transplantation. For the purpose of validation, patients were categorized into a non-obese group (baseline BMI <25 kg/m2) and obese group (baseline BMI ≥25 kg/m2). Analysis was repeated using a lower BMI cut-off value and the patients were categorized into normal group (baseline BMI <23 kg/m2) and overweight group (baseline BMI ≥23 kg/m2). Further analysis was also carried out with patients categorized into four groups based on their BMI quartiles. Follow-up data were analyzed until 31 March 2008. Data including the demographic and clinical variables of transplantation were collected from patients’ records. BMI (in kg/m2) was ascertained at the time of kidney transplantation, at 1 and 5 years post-transplant. The primary end-point was overall graft survival, which was defined as the time from transplantation until death, return to dialysis or re-transplantation. Additionally, patient survival and death-censored graft survival were investigated.