Quantitative chest CT for subtyping chronic lung allograft dysfunction and its association with survival

Chronic lung allograft dysfunction (CLAD) is a major cause of mortality in lung transplant recipients. CLAD can be sub‐divided into at least 2 subtypes with distinct mortality risk characteristics: restrictive allograft syndrome (RAS), which demonstrates increased overall computed tomography (CT) lung density in contrast with bronchiolitis obliterans syndrome (BOS), which demonstrates reduced overall CT lung density. This study aimed to evaluate a reader‐independent quantitative density metric (QDM) derived from CT histograms to associate with CLAD survival. A retrospective study evaluated CT scans corresponding to CLAD onset using pulmonary function tests in 74 patients (23 RAS, 51 BOS). Two different QDM values (QDM1 and QDM2) were calculated using CT lung density histograms. Calculation of QDM1 includes the extreme edges of the histogram. Calculation of QDM2 includes the central region of the histogram. Kaplan‐Meier analysis and Cox regression analysis were used for CLAD prognosis. Higher QDM values were significantly associated with decreased survival. The hazard ratio for death was 3.2 times higher at the 75th percentile compared to the 25th percentile using QDM1 in a univariate model. QDM may associate with CLAD patient prognosis.     

Caring for the carer: a systematic review of pure technology-based cognitive behavioral therapy (TB-CBT) interventions for dementia carers

Background: Face-to-face delivery of CBT is not always optimal or practical for informal dementia carers (DCs). Technology-based formats of CBT delivery (TB-CBT) have been developed with the aim to improve client engagement and accessibility, and lower delivery costs, and offers potential benefits for DCs. However, research of TB-CBT for DCs has maintained heavy reliance on therapist involvement. The efficacy of pure TB-CBT interventions for DCs is not currently established

Methods: A systematic review of trials of pure TB-CBT intervention for DCs from 1995 was conducted. PsycINFO, Cochrane Reviews, Scopus and MedLine databases were searched using key terms related to CBT, carers and dementia. Four hundred and forty two articles were identified, and inclusion/exclusion criteria were applied; studies were only retained if quantitative data was available, and there was no active therapist contact. Four articles were retained; two randomized and two waitlist control trials. Methodological and reporting quality was assessed. Meta-analyses were conducted for the outcome measures of caregiver depression.

Results: Meta-analysis revealed small significant post-intervention effects of pure TB-CBT interventions for depression; equivalent to face-to-face interventions. However, there is no evidence regarding long-term efficacy of pure TB-CBT for DCs. The systematic review further identified critical methodological and reporting shortcomings pertaining to these trials

Conclusions: Pure TB-CBT interventions may offer a convenient, economical method for delivering psychological interventions to DCs. Future research needs to investigate their long-term efficacy, and consider potential moderating and mediating factors underpinning the mechanisms of effect of these programs. This will help to provide more targeted interventions to this underserviced population.     

A biomechanical model of the effect of subtalar arthroereisis on the adult flexible flat foot

OBJECTIVE: The hypothesis tested was that the increased load on the medial arch in the adult flat foot can be reduced through a 6 mm subtalar arthroereisis. DESIGN: A three-dimensional multisegment biomechanical model was used in conjunction with experimental data and data from the literature. BACKGROUND: Biomechanical models have been used to study the plantar fascia, medial arch height, subtalar motion, medial displacement calcaneal osteotomy and distribution of forces in the foot. METHODS: Responses of a normal foot, a flat foot, and a flat foot with a subtalar arthroereisis to an applied load of 683 N were analyzed and the distribution of support among the metatarsal heads and the moment about various joints were computed. RESULTS: The flattened foot results in an increase in the load on the head of the first metatarsal from 10% to 24% of the body weight, and an increase in the moment about the talo-navicular joint from 3.4 to 11.9 Nm. Insertion of a 6 mm cylinder into the sinus tarsi, subtalar arthroereisis, results in a shift of the load back toward the lateral column, decreasing the load on the first metatarsal to 6% of the body weight and decreasing the moment about the talo-navicular joint to 6.0 Nm. CONCLUSIONS: Our analysis indicates that a 6 mm subtalar arthroereisis in an adult flat foot model decreases the load on the medial arch.     

Relationship of perceived job strain and workplace support to antenatal depressive symptoms among pregnant employees in Taiwan

Most Taiwanese women continue to work throughout pregnancy. Few studies have investigated the prevalence of antenatal depressive symptoms in employed women and their relationship with work-related factors. We explored the relations of work-related factors, including perceived job strain and workplace support, to depressive symptoms among pregnant Taiwanese employees. During 2015–2016, we interviewed 153 employees in their third trimester of pregnancy using questionnaires to collect data on demographics, pregnancy status, physical conditions, work-related factors, family function, the Edinburgh Postnatal Depression Scale (EPDS), and health-related quality of life (HRQoL). The prevalence of antenatal depressive symptoms, based on EPDS scores≥13, was 13.7%. Pregnant employees with depressive symptoms had lower Family APGAR scores (p < 0.0001) and lower scores on all scales of the HRQoL (p < 0.05). Controlling for covariates, work-related feelings of stress and distress were associated with increased odds of antenatal depressive symptoms (Odds Ratio [OR] = 4.7, 95% confidence Interval [95% CI] = 1.3–19.9). Feeling tired at work (OR = 9.1, 95% CI = 2.3–47.0) and lack of support from colleagues (OR = 16.7, 95% CI = 2.9–53.1) were significantly associated with antenatal depressive symptoms. Such information will facilitate implementation of supportive workplace climates for pregnant employees by employers, supervisors, and occupational and environmental health nurses, which may help improve the health of pregnant employees.     

Enhanced stability of horseradish peroxidase encapsulated in acetalated dextran microparticles stored outside cold chain conditions

Micro- and nanoparticles have been shown to improve the efficacy of safer protein-based (subunit) vaccines. Here, we evaluate a method of improving the vaccine stability outside cold chain conditions by encapsulation of a model enzyme, horseradish peroxidase (HRP), in an acid-sensitive, tunable biodegradable polymer, acetalated dextran (Ac-DEX). Vaccines that are stable outside the cold chain would be desirable for use in developing nations. Ac-DEX particles encapsulating HRP were prepared using two different methods, probe sonication and homogenization. These particles were stored under different storage conditions (-20 °C, 4 °C, 25 °C or 45 °C) for a period of 3 months. On different days, the particles were characterized for various physical and chemical measurements. At all conditions, Ac-DEX particles remained spherical in nature, as compared to PLGA particles that fused together starting at day 3 at 45 °C. Furthermore, our results indicated that encapsulation of HRP in Ac-DEX reduces its storage temperature dependence and enhances its stability outside cold chain conditions. Homogenized particles performed better than probe sonicated particles and retained 70% of the enzyme's initial activity as compared to free HRP that retained only 40% of the initial activity after 3 months of storage at 25 °C or 45 °C. Additionally, HRP activity was more stable when encapsulated in Ac-DEX, and the variance in enzyme activity between the different storage temperatures was not observed for either particle preparation. This suggests that storage at a constant temperature is not required with vaccines encapsulated in Ac-DEX particles. Overall, our results suggest that an Ac-DEX based micro-/nanoparticles system has wide applications as vaccines and drug delivery carriers, including those in developing nations.     

Mosaic ACVRL1 and ENG mutations in hereditary haemorrhagic telangiectasia patients

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder caused by mutations in the ACVRL1, ENG, and SMAD4 genes. HHT is commonly characterised by small arteriovenous malformations (AVMs) known as telangiectasias of the skin, oral or gastrointestinal mucosa, as well as larger AVMs of solid organs (lungs, liver, brain). However, the manifestations of HHT are extremely variable. Two patients with no family history of HHT and strikingly different clinical presentations, who are mosaic for mutations in the ACVRL1 or ENG gene, are reported here. These cases represent the first report of mosaicism in patients clinically affected with classical HHT and pulmonary arterial hypertension, and suggest the need for awareness of mosaicism when performing clinical testing for this disorder.     

Toward efficient biomechanical-based deformable image registration of lungs for image-guided radiotherapy

Both accuracy and efficiency are critical for the implementation of biomechanical model-based deformable registration in clinical practice. The focus of this investigation is to evaluate the potential of improving the efficiency of the deformable image registration of the human lungs without loss of accuracy. Three-dimensional finite element models have been developed using image data of 14 lung cancer patients. Each model consists of two lungs, tumor and external body. Sliding of the lungs inside the chest cavity is modeled using a frictionless surface-based contact model. The effect of the type of element, finite deformation and elasticity on the accuracy and computing time is investigated. Linear and quadrilateral tetrahedral elements are used with linear and nonlinear geometric analysis. Two types of material properties are applied namely: elastic and hyperelastic. The accuracy of each of the four models is examined using a number of anatomical landmarks representing the vessels bifurcation points distributed across the lungs. The registration error is not significantly affected by the element type or linearity of analysis, with an average vector error of around 2.8 mm. The displacement differences between linear and nonlinear analysis methods are calculated for all lungs nodes and a maximum value of 3.6 mm is found in one of the nodes near the entrance of the bronchial tree into the lungs. The 95 percentile of displacement difference ranges between 0.4 and 0.8 mm. However, the time required for the analysis is reduced from 95 min in the quadratic elements nonlinear geometry model to 3.4 min in the linear element linear geometry model. Therefore using linear tetrahedral elements with linear elastic materials and linear geometry is preferable for modeling the breathing motion of lungs for image-guided radiotherapy applications.     

Th1 and Th17 Cells Induce Proliferative Glomerulonephritis

Th1 effector CD4+ cells contribute to the pathogenesis of proliferative and crescentic glomerulonephritis, but whether effector Th17 cells also contribute is unknown. We compared the involvement of Th1 and Th17 cells in a mouse model of antigen-specific glomerulonephritis in which effector CD4+ cells are the only components of adaptive immunity that induce injury. We planted the antigen ovalbumin on the glomerular basement membrane of Rag1^−/− mice using an ovalbumin-conjugated non-nephritogenic IgG1 monoclonal antibody against α3(IV) collagen. Subsequent injection of either Th1- or Th17-polarized ovalbumin-specific CD4+ effector cells induced proliferative glomerulonephritis. Mice injected with Th1 cells developed progressive albuminuria over 21 d, histologic injury including 5.5 ± 0.9% crescent formation/segmental necrosis, elevated urinary nitrate, and increased renal NOS2, CCL2, and CCL5 mRNA. Mice injected with Th17 cells developed albuminuria by 3 d; compared with Th1-injected mice, their glomeruli contained more neutrophils and greater expression of renal CXCL1 mRNA. In conclusion, Th1 and Th17 effector cells can induce glomerular injury. Understanding how these two subsets mediate proliferative forms of glomerulonephritis may lead to targeted therapies.Although proliferative and crescentic glomerulonephritides occur in different primary renal diseases and are an important component of several systemic diseases, features of human renal biopsies suggest some common effector pathways. In most cases of rapidly progressive GN there is evidence for an important role for cellular immune effectors: T cells, macrophages, and neutrophils,^1–3 a role confirmed in animal models.^4–7 CD4+ T cells are key components of renal injury.^4,8 When activated, CD4+ cells tend to differentiate into subsets (T helper cells—Th1, Th2 and Th17) that engage immune effectors in different ways. In proliferative forms of GN, T cells direct adaptive immune responses that drive glomerular disease, but also, in rapidly progressive GN, CD4+ cells themselves accumulate in glomeruli as effectors. These effector T helper cells activate innate effector cells, predominantly neutrophils and macrophages, and activate and damage intrinsic renal cells.In GN, the variable Th1-Th2 predominance of responses influences the histologic patterns and severity of GN.⁹ Th1 cells, which secrete IFNγ and activate macrophages, are important in some forms of experimental proliferative GN. Th2 cells, characterized by IL-4 production, promote humoral immunity and are important in several forms of GN, but there is little evidence that Th2 cells play primary roles as effector cells within glomeruli in rapidly progressive GN. A binary Th1/Th2 model explains many of the differences in the patterns of immune responses in GN. However, there are discrepancies¹⁰ that might be explained by defining a role for a third major subset, Th17 cells, characterized by the production of IL-17A. Its biology has recently been comprehensively reviewed.¹¹ Th17 subset effects potentially relevant to rapidly progressive GN include direct effects on neutrophils and stimulating the production of neutrophil chemoattractants by tissue cells. Thus, in most rapidly progressive types of GN, cell-mediated injury, a key component of injury, may be directed by the Th17 subset, the Th1 subset, or both subsets.Although antigen-specific T cells are critical to adaptive immune responses, the cells themselves are relatively infrequent. T cell receptor (TcR) transgenic mice help define the contributions of different antigen-specific T helper cell subsets in organ-specific disease.^12–14 In the studies presented here we have established a new antigen-specific model of GN. Ovalbumin (OVA)-specific OT-II TcR transgenic CD4+ cells¹⁵ are polarized ex vivo under Th1- or Th17-inducing conditions. Effector cells are transferred into recombination activating gene-1 deficient (Rag1^−/−) mice with OVA planted in their glomeruli by injecting an OVA conjugate. OVA is conjugated to a mouse IgG1 mAb binding to α3(IV) collagen in murine glomerular basement membrane (GBM). The mAb-OVA conjugate dose is capable of planting significant OVA in glomeruli as an antigen to induce effector responses, but is insufficient to induce significant histologic or functional injury as an antibody. This model allows us to understand effector CD4+ T cell and Th subset-induced injury, with no effects from CD8+ cells or B cells.CD4+ cells, isolated from OVA-specific TcR transgenic (OT-II) mice and cultured under Th1 or Th17 priming conditions (see Concise Methods), were confirmed to be Th1 or Th17 by cytokine production before transfer. Th1 polarized cells expressed IFNγ, whereas no IL-17A or IL-4 production was detected (Figure 1A). Th17 polarized cells were strong IL-17A producers, showing only weak IFNγ production, with >20% of cells producing IL-17A, but few IFNγ or double-positive cells (Figure 1B). To plant OVA in glomeruli, the mAb 8D1, a non-nephritogenic, murine IgG1 binding to mouse α3(IV)NC1,¹⁶ was conjugated to OVA and purified by size-exclusion chromatography so that no free OVA or unconjugated 8D1 mAb remained, confirmed by Western blotting (Figure 1C). Antigen-specific CD4+ cells recognized OVA bound to the 8D1 anti-GBM mAb. Culture of CFSE-labeled naive OT-II cells incubated with the 8D1-OVA conjugate enhanced their survival (30% to 40% survival after 72 h versus 5% to 6% with unconjugated antibody) and induced OT-II cell proliferation (72 h: 27% of cells, up to 4 cycles, Figure 1D). OT-II cells incubated with unconjugated 8D1 did not proliferate (Figure 1E). After intravenous injection, 8D1-OVA conjugates bound to the GBM in a linear manner; no fluorescence signal was observed after transfer of Th1 cells without 8D1-OVA (Figure 1G). Western blotting showed OVA in the kidney after injection of 8D1-OVA conjugate (Figure 1H). Lungs from 8D1-OVA-injected mice were weakly positive for mouse IgG, whereas no IgG was detected in the spleen or liver (detecting antibody titer 1:100) 3 or 21 d after injection. Mouse IgG was not detected in sera (ELISA, dilution 1:100) at day 3 or day 21. As expected (given the transfer of only CD4+ cells to Rag1^−/− mice), no anti-OVA antibodies in sera were detected in recipient mice (data not shown).Open in a separate windowFigure 1.Differentiation of OVA-specific OT-II Th1 and Th17 cells, antibody-OVA conjugation, glomerular IgG and intrarenal OVA detection, and recipient immune responses after cell transfer. (A) After stimulating naive OT-II cells with OVA in a Th1 environment, IFNγ was produced and intracellular cytokine staining of CD4+ cells demonstrated strong IFNγ staining with minimal IL-17A or IL-4. (B) Culturing cells in a Th17-stimulating environment led to strong IL-17A production, whereas cells stained positive for IL-17A but not IL-4, and only 2% of cells produced IFNγ. (C) Chromatographic profile of 8D1-OVA conjugation. The numbers 1 to 7 represent fractions collected for analyses by Western blotting, which confirmed that all OVA-conjugated fractions contained OVA and IgG (lanes 1–6), whereas unconjugated fractions (represented as “Un”) contained IgG alone. The lane labeled “M” contained molecular weight markers. (D and E): 8D1-OVA was recognized by OT-II cells because multiple cycles of proliferation of cultured naive OT-II cells (D) were seen with 8D1-OVA conjugate and (E) not seen with unconjugated antibody. Strong linear IgG staining of glomeruli was seen after (F) the administration of 8D1-OVA to Rag1^−/− mice, but not after (G) the injection of Th1 cells without antibody. Western blotting of homogenized kidney (H) 24 h after the administration of 8D1-OVA demonstrated OVA in the kidneys (labeled as OVA-Ab); this was not seen after the administration of unconjugated antibody (labeled as Un Ab). (I) Systemic immune responses of recipient Rag1^−/− mice at 21 d assessed by splenic cytokine production demonstrated enhanced IFNγ production in mice given 8D1-OVA and Th1 cells, with enhanced IL-17A production by mice receiving 8D1-OVA and Th17 cells. (J) DTH to OVA (at 21 d) was induced only in mice given 8D1-OVA and Th1 cells. *P < 0.05, ***P < 0.001.To determine whether transfer of either Th1 or Th17 antigen-specific effector cells induces glomerular injury, 8D1-OVA conjugate was administered intravenously to Rag1^−/− mice (lacking adaptive immunity). Three hours later, 5 × 10⁶ Th1 or Th17 cells were injected intravenously. Groups of mice injected with 8D1-OVA alone (without cells) or Th1 cells alone (without 8D1-OVA) served as controls. At 21 d, the injected T cells largely maintained their initial phenotype, because host splenocytes from mice given Th1 cells showed enhanced OVA-stimulated IFNγ production whereas IL-17A production was enhanced in mice given Th17 cells (Figure 1I). Dermal-delayed-type hypersensitivity (DTH) was induced by footpad injection of OVA and measured after 24 h. Only mice that received the 8D1-OVA conjugate and Th1 polarized cells developed dermal DTH (Figure 1J), a classical Th1 response.¹⁷After planting OVA in glomeruli, administration of Th1 or Th17 cells induced glomerular disease. Urinary albumin excretion was not increased in mice given 8D1-OVA conjugate alone or Th1 cells alone, but Th1 or Th17 cells with 8D1-OVA induced significant albuminuria (Figure 2A). Albuminuria was consistent throughout the time course of the study in the Th17 group, whereas in the Th1 group there was a progressive increase in albuminuria until day 21 (Figure 2B). Control mice given Th1 cells alone or the 8D1-OVA conjugate alone exhibited only mild histologic changes (no crescent formation, fibrinoid necrosis, or hyalinosis). Analysis of histologic injury demonstrated substantially more abnormal glomeruli in the mice given 8D1-OVA conjugate with Th1 or Th17 cells compared with control groups (Figure 2C). Th1 and Th17 (+8D1-OVA) recipients developed proliferative GN, [glomerular hypercellularity: 8D1-OVA and Th1 cells: 32.1 ± 1.0 cells/glomerular cross section (c/gcs), 8D1-OVA and Th17 cells: 29.8 ± 1.1 c/gcs, 8D1-OVA alone: 21.3 ± 0.2 c/gcs, Th1 cells alone: 18.9 ± 2.0 c/gcs; P < 0.001]. Representative kidney sections from each group are shown (Figure 2, D through G). Crescent formation and fibrinoid necrosis, although seen in only a few glomeruli, was observed exclusively in mice given 8D1-OVA conjugate and Th1 cells (5.5 ± 0.9% at day 21; Figure 2, H and I). No crescent formation was observed in mice receiving 8D1-OVA conjugate and Th17 cells. Mice did not develop significant renal impairment (measured by BUN; data not shown).Open in a separate windowFigure 2.Renal injury in mice injected with 8D1-OVA conjugate, then either Th1 or Th17 cells. (A) Mice given 8D1-OVA conjugate or Th1 cells alone did not develop albuminuria above values for noninjected Rag1^−/− mice (dotted line). At 21 d, albuminuria was increased in mice given 8D1-OVA and Th1 cells or 8D1-OVA and Th17 cells. (B) In mice given 8D1-OVA and Th17 cells, albuminuria had plateaued by day 7 and did not progress. In mice given 8D1-OVA and Th1 cells there was a progressive rise in albuminuria. (C) Histologic injury was significant in mice given 8D1-OVA and either Th1 or Th17 cells. Representative glomeruli from mice given (D) 8D1-OVA alone, (E) Th1 cells alone, (F) 8D1-OVA and Th1 cells, and (G) 8D1-OVA and Th17 cells are shown. (H and I) Crescentic injury and fibrinoid necrosis were only seen in mice given 8D1-OVA and Th1 cells. ***P < 0.001Recruitment and activation of leukocyte subpopulations differed in mice administered Th1 or Th17 cells (Figure 3A). Although glomerular CD4+ cell and macrophage numbers were similarly increased in mice given 8D1-OVA conjugate and either Th1 or Th17 cells at day 21, more neutrophils were found in mice given 8D1-OVA and Th17 cells compared with mice given 8D1-OVA and Th1 cells. Interstitial leukocyte infiltrates followed a similar pattern (Figure 3B). Consistent with the finding of increased neutrophils in kidneys of mice receiving Th17 cells, renal mRNA expression of the primary neutrophil attracting chemokine CXCL1 was elevated (Figure 3C). Th17 cells attract neutrophils¹⁸ and in vitro studies have shown that neutrophil recruitment is achieved via production of CXCL8, the human homologue of CXCL1, by Th17 cells.¹⁹ It is therefore likely that at least some of the Th17-induced renal injury is mediated by neutrophils. In mice receiving 8D1-OVA and Th1 cells, macrophages were likely to be more activated; only these mice developed dermal DTH and increased expression of mRNA for the macrophage chemoattractants CCL2 and CCL5 (Figure 3, D and E), which have been associated with experimental crescentic GN.²⁰ Furthermore, type 2 nitric oxide synthase (NOS2/iNOS) mRNA, a marker of macrophage activation²¹ and urinary nitrate, a marker of intrarenal macrophage NOS2 production, were increased in this group (Figure 3, F and G).Open in a separate windowFigure 3.Leukocytes in kidneys of mice with either Th1- or Th17-induced injury 21 d after cell transfer. (A) Glomerular CD4+T cells, neutrophils, and macrophages were increased in mice given 8D1-OVA and Th1/Th17 cells. Neutrophil recruitment was incrementally increased in mice given 8D1-OVA and Th17 cells compared with 8D1-OVA and Th1 cells. (B) A similar pattern of recruitment was seen in the cortical interstitium. Renal chemokine mRNA expression demonstrated (C) enhanced CXCL1 mRNA in mice given 8D1-OVA and Th17 cells, whereas (D) CCL2 and (E) CCL5 were increased in mice given 8D1-OVA and Th1 cells. (F and G) NOS2 and urinary nitrate, markers of macrophage activation, were increased in mice receiving 8D1-OVA and Th1 cells. For mRNA, values for the 8D1-OVA alone group are presented as 1. *P < 0.05, **P < 0.01, ***P < 0.001.Further studies were performed 3 d after cell transfer. At this time point, albuminuria was present in mice receiving 8D1-OVA conjugate and Th17 cells, but not 8D1-OVA conjugate and Th1 cells (Figure 4A), and a higher proportion of glomeruli were abnormal in mice that had received Th17 cells (Figure 4B). Therefore, Th17-induced glomerular injury occurred earlier than Th1-induced injury. Leukocytes were present in glomeruli (Figure 4C) with increased numbers of neutrophils in glomeruli of mice receiving Th17 cells (compared with Th1 cell recipients), whereas Th1 cell recipients exhibited more macrophages. At day 3, these findings were glomerulo-specific; differences between Th1 and Th17 cell recipients were not seen in the interstitium (Figure 4D).Open in a separate windowFigure 4.Renal disease in mice 3 d after injection with 8D1-OVA and either Th1 or Th17 cells. (A) Pathologic albuminuria (dotted line represents values for noninjected Rag1^−/− mice) and (B) increased numbers of abnormal glomeruli were evident in mice that received 8D1-OVA and Th17 cells. (C) Leukocyte recruitment to glomeruli demonstrated CD4+ cells (more in mice receiving Th1 cells), with comparatively more neutrophils in glomeruli of Th17 cell recipients and more macrophages in glomeruli of Th1 cell recipients. (D) Interstitial leukocytes were similar in Th1 and Th17 cell recipients 3 d after cell transfer. *P < 0.05, **P < 0.01, ***P < 0.001.These studies used Rag1^−/− mice as recipients of effector antigen-specific Th1 or Th17 cells. Because these mice do not possess T or B cells, OVA planted in glomeruli cannot induce CD8+ or B cell responses, and regulatory T cells are unable to influence the pattern of injury. A major advantage of this strategy is that Th1- and Th17-mediated injury can be assessed in a pure experimental system. However, T cells transferred into Rag1^−/− mice can undergo homeostatic expansion, and it is possible that the transferred Th1 cells might have expanded more rapidly than Th17 cells. Recently, studies in experimental type 1 diabetes induced by transfer of cells from a TcR transgenic mouse specific for an islet autoantigen showed conversion of Th17 cells to a Th1 phenotype after transfer.^22,23 Although our Th17 polarized OT-II cells, specific for a foreign antigen, showed some IFNγ production after 21 d, they were still capable of producing IL-17A. Furthermore, dermal DTH and renal disease were different in Th1 recipients compared with the Th17 recipients at 21 d, supporting the maintenance of separate phenotypes after transfer. Although the studies presented here are the first to demonstrate a role for Th17 and Th1 cells in the same experimental system, other studies^24–26 have used genetically deficient mice to implicate Th17 cells in experimental renal disease.These studies describe a novel model of cell-mediated proliferative GN for which adaptive components are only effector antigen-specific CD4+ T cells. They demonstrate that both Th1 and Th17 cells can induce proliferative GN. Th17 cells induce albuminuria early, with persistent accumulation of leukocytes. Administration of Th1 cells lead to a slower rise in albuminuria, but more macrophage activation and DTH-like injury, including, in some glomeruli, crescent formation and fibrinoid necrosis. It is likely that Th1 and Th17 responses play a role in proliferative forms of GN and both represent potential therapeutic targets.