In addition, I found many eosinophilic inclusion bodies in small neurons of the deeper layers of the cerebral cortex. Then, I wondered what these bodies were. Prior PD0325901 to that time, it was thought that Lewy bodies only rarely occurred in the cerebral cortex. Thereafter, I also found many similar cortical eosinophilic bodies in the brain of another patient2 with similar clinical symptoms. I became interested in these cortical eosinophilic bodies. Morphologically these bodies were similar to, but somewhat different from, brain stem Lewy

bodies. Therefore, I could not identify these cortical eosinophilic bodies as Lewy bodies. Based on histochemical and electron microscopic examinations, I demonstrated that these cortical eosinophilic bodies were cortical Lewy bodies. In 1978, we reported a second paper2“Lewy bodies in cerebral cortex” in Acta Neuropathologica, based on our three cases including the first case. In that report, the close relationship between cortical Lewy bodies and neuronal cell death was for the first time

indicated by showing six developmental stages of cortical Lewy bodies. In addition, we pointed out for the first time that LBH589 in vivo the amygdala and claustrum are also predilection sites for Lewy bodies. Following these papers, some similar cases were reported in Japan. In the USA, a Japanese neuropathologist, Okazaki, and his colleagues5 reported two similar American autopsied cases without Alzheimer pathology Progesterone in 1961, but these cases had not received attention until our citation of their paper in our first paper.1 In addition, Forno et al.6 also reported a similar American case in 1978. In 1979, we reported3 two similar German cases when I was at the Max-Planck Institute of Psychiatry in Munich. These were the first DLBD cases reported in Europe. In 1984, we proposed4 the term “diffuse Lewy body disease (DLBD)” based on our 11 autopsies

including Japanese, German and Austrian cases. As we proposed it in 1980, 11 DLBD was thought to be a type of “Lewy body disease”. We classified Lewy body disease into three types: brainstem type, traditional type and diffuse type. The diffuse type is now considered DLBD, while the brain stem type is considered PD. After our proposal of DLBD in 1984, this disease received more attention among European and American researchers. In 1990, I reviewed 37 autopsied DLBD cases reported in Japan.9 Then I classified these cases into two forms: a common form with a more or less Alzheimer pathology, and a pure form without such findings. In addition, I pointed out that the clinical features differed between the two forms. In the common form, all cases showed presenile or senile onset, and the chief clinical feature was progressive dementia, followed by parkinsonism in 70% of cases, while in the pure form most cases showed early onset and the chief clinical symptom was parkinsonism, followed by dementia.

This protein is expressed predominantly at both the mRNA and protein levels in highly virulent strains. Moreover, its enzymatic activity is altered by specific PDI inhibitors which profoundly affect parasite growth [20]. Furthermore, Ben Achour et al. showed

that Lm parasites deleted for Transmembrane Transporters activator the lmpdi gene are non-virulent in experimental leishmaniasis induced in BALB/c mice (unpublished data). However, unexpectedly, our results indicated that in LV clones, the lmpdi gene deletion, although having no effect on parasite burden, was associated with an increase of the infection rate. These unexpected results could be attributed to the fact that virulence of Lm clones as well as lmpdi-deleted clones was established in mice. It is well known that relating results observed in experimental murine leishmaniasis to humans is not always obvious. Alternatively, a decrease in virulence of lmpdi-deleted parasites in the human host, as shown in mice, cannot be excluded, as several factors involved in in-vivo Leishmania-DCs interactions are absent in in-vitro experiments. Conversely, we cannot exclude that differential expression of the lmpdi gene between HV and LV parasites could be associated with a differential role on human DC infectivity. Overall, our results suggest

that there is a correlation between virulence of Lm clones and ability to infect and to replicate in human myeloid GDC-0941 order DCs. Moreover, LmPDI protein may be associated with DC infectivity. Due to its key role in assisting Leishmania protein folding via its capacity to catalyse formation, breakage and rearrangement of disulphide bonds in nascent polypeptides [20,24], LmPDI could be implicated either directly or indirectly in attachment, internalization or intracellular multiplication of Lm parasites.

Contradictory data are reported concerning the in-vitro infectivity of human DCs by Leishmania parasites. Comparable levels of parasite uptake by human DCs were reported C59 for Lm, L. tropica and L. donovani promastigotes [11], whereas other authors showed lower infectivity for two virulent L. donovani strains [13]. These results could be explained in part by variability in the virulence of the Leishmania strains. Our results are in agreement with those of previous studies on the capacity of Lm to infect human DCs [6,11,25]. However, to our knowledge, this is the first demonstration of a significant difference in the in-vitro infectivity of human DCs by Lm strains differing by their virulence. Recently, it was reported that DCs control the intracellular growth of mycobacteria strains differently, suggesting variability in the cell-to-cell spread outcome during the first step of infection [26]. The second goal of this study was to analyse the impact of Lm virulence on DC differentiation. Our data showed that Lm clones were able to alter DC differentiation by down-regulating CD1a expression, whatever their virulence. L.

tuberculosis infection [8]. This importance is underscored by the observation that children with hereditary IFN-γ receptor 1 deficiency are prone to M. tuberculosis infection or to dissemination of BCG after vaccination [9–11]. Furthermore, IFN-γ treatment has shown promising results in patients with multidrug-resistant PTB [12]. IL-22 belongs to the IL-10 family, which signals through a receptor complex see more IL-22R1/IL-10R2 [13–15]. IL-10R2 is highly expressed on immune cells. However, IL-22R1 is specifically expressed on epithelial and some fibroblast

cells in peripheral tissues such as gastrointestinal, respiratory system and skin [16]. IL-22 can induce tissue expression of acute inflammatory proteins, mucins or antimicrobial peptides, which are important for tissues to maintain their integrity during chronic inflammation [17]. IL-17 is found to induce human fibroblasts and bronchial epithelial cells to express IL-8 and G-CSF, triggering recruitment of neutrophils check details to the lung and facilitating granuloma formation [18–20]. IL-17 can also initiate recruitment of Th1 cells to the lung by upregulating CXCL9, CXCL10 and CXCL11, which can eventually control bacterial growth and defence after M. tuberculosis infection

[21]. Patients with tuberculous pleurisy (TBP) have a relatively strong immune response against M. tuberculosis infection [22], and the disease results from delayed hypersensitivity involving macrophages, T cells and cytokines. Therefore, we took TBP as a relevant model to study

the immune inflammatory response at the local site of M. tuberculosis infection. ESAT-6 and CFP-10 are used to test specific responses because these antigens may be critical in the development of protective immunity to M. tuberculosis infection. They are present in all M. tuberculosis and pathogenic Mycobacterium bovis strains but lacking in all BCG strains [23]. Our data demonstrate for the first time that ESAT-6-, CFP-10- and BCG-specific Th1, Th22 and Th17 cells are present at the local site of infection in patients with TBP and these cells may play an important role in the local protective cellular immunity. Subjects.  The study was conducted among 23 patients with TBP: 11 men and 12 women aged 19–83 years (mean = 39.82 years). All Adenylyl cyclase participants were from the Chest Hospital of Guangzhou, and they had written informed consent. The diagnosis of tubercular pleural effusion was made on the basis of the following criteria: medical history, physical examination, chest X-ray, isolation of M. tuberculosis from the pleural fluid or tissue, a smear positive for acid-fast bacilli from the pleural fluid or tissue or a positive mycobacterium culture. None of the patients was on anti-TB treatment at the time of enrolment in the study. Exclusion criteria included positive HIV test or the presence of concurrent infectious diseases. Pleural fluid samples were obtained during therapeutic thoracentesis.

Hookworm, because of its high prevalence but relatively low mortality, causes a greater burden of DALYs (1·83 million) than schistosomiasis (1·76 million) or trypanosomiasis (1·60 million) (2). Two recent events have reinvigorated immunological studies on hookworms – the funding of the Human Hookworm Vaccine Initiative by the Bill and learn more Melinda Gates Foundation (http://www.sabin.org/vaccine-development/vaccines/hookworm), and the discovery that parasitic helminths, and hookworms in particular, can suppress inflammation associated with autoimmune and allergic diseases – a phenomenon that is embodied by the Hygiene Hypothesis.

Recent and past contributions to these and other aspects of hookworm immunology have involved talented researchers from many different countries, but in this review, we will focus

particularly on the work of Australian researchers. Antibodies of the isotypes IgG1, IgG4, IgM, IgD, IgA and IgE from hookworm-endemic (both the human hookworms N. americanus and the zoonotic dog hookworm Ancylostoma caninum) populations have all been shown to bind to hookworm antigens (5). In experimental hookworm infections, parasite-specific IgM is detectable 6 weeks after infection, with parasite-specific IgG detectably increased BAY 57-1293 concentration 8 weeks after infection (6–9). IgE responses in experimental human infections appear to develop slowly over a number of exposures, and the IgE response is generally undetectable in primary infections (8,9). As a result of its protective role in many helminth infections, IgE has been of particular interest to researchers. In the 1970s, David Grove and colleagues studied the role of IgE in N. americanus infections in the highlands of Papua New Guinea. They were the first to show that IgE, whether it be parasite specific or polyclonal, afforded protection against hookworm infection Ribonucleotide reductase (10,11).

Further evidence of the protective role of IgE in hookworm infection comes from vaccine studies, where levels of IgE against the vaccine candidate antigen Na-ASP-2 (ancylostoma secreted protein-2) in endemic populations from Brazil negatively correlate with infection intensity, while IgG4 against ASP-2 positively correlates with infection intensity (12). In filariasis and schistosomiasis, parasite-specific IgG4 correlates with a suppressed ‘modified TH2’ response, able to be differentiated from the parasite-killing (but often more pathogenic) IgG1 or IgE immune responses (13). A similar paradigm may exist in hookworm infection, and indeed, IgG4 specific to hookworm antigens is the best serological predictor of infection (14,15), implying a modified TH2 response is almost universal in hookworm infection. Therefore, if the immune response to hookworm is skewed away from the modified TH2 IgG4 response to a protective TH2 IgE response, immunity to the parasite may be possible.

Background: ATHOME enrolment is organised by treating physicians for patients after a minimum 12 AAG or 3 VAG in hospital infusions. Methods: The ATHOME Program Coordinator arranges for an IV administration trained registered nurse to deliver, prepare, administer and monitor infusion safety in the home or workplace. Physicians receive written reports after each infusion. Records of infusion timings, retention rates and patient numbers are collated by the nurses and managed by the ATHOME Coordinator. Results: ATHOME commenced in Australia July 2010 for AAG patients. In May 2013

it was extended to ITF2357 solubility dmso VAG patients. Total enrolments to 28 February 2014 were 30 AAG and 12 VAG patients. Patient retention to ATHOME over the length of the program has been 86.7% and 75.0% with an adherence of 97.9% and 98.1% of planned infusions administered, 89.7% and 86.9% delivered within 2 days of due date for AAG and VAG respectively. Conclusions: ATHOME infusion service successfully offered enrolled patients the convenience and flexibility to receive their treatment in the home or workplace environment with high adherence. 227 COCA COLA? THE NEW TOBACCO

WE HOY1, D EDDY2, RW MANNING3, L TUNGATALUM4, PW HOY5, SA MOTT1, PA BALL6 1Centre for Chronic Disease, Raf inhibitor The University of Queensland, Brisbane, QLD; 2Formerly Nguiu Ullintjinni Association, Tiwi Islands, NT; 3RWM Consultancy, Darwin, NT; 4Tiwi Land Council, Tiwi Islands, NT; 5Formerly MSC, Darwin Thiamet G Diocese, NT; 6Charles Darwin University, Darwin, NT, Australia Aim: To highlight volumes

of sales of Coca-Cola in remote Aboriginal communities. Background: Aboriginal people in remote areas are impoverished, poorly educated, poorly nourished, have limited choices and pay high prices for every commodity. Early life malnutrition enhances susceptibility to chronic disease, which is amplified by a diet of highly processed micronutrient-deficient calorie-dense foods. The WHO recommends that sugars constitute <10% (soon potentially <5%) of energy intake. Brimblecombe recently estimated, in three remote communities, that sugars constituted about 30% of energy intake. Our observations. In a 2011 store audit in a separate study community, with the highest CV death and renal failure rates in Australia, soft drinks, sweets and ice-creams accounted for 46% of spending on consumables, exclusive of alcohol and cigarettes. Specifically, 108,000 litres of Coca-Cola Amatil (CCA) softdrink were sold in six months, or >16 litres per month for everyone age 15+ years. On enquiry, CCA’s Board Chairman cited corporate resolve to provide a full range of choices to even the most disadvantaged Australians. In 2007, CCA’s website nominated the NT as the global leader in per capita Coke consumption.

Although environmental factors, such as high altitude and smoking, play a role, genetic factors undoubtedly contribute. Indeed, in humans, ~37% SAHA HDAC concentration of fetal growth restriction can be explained by fetal genetic factors [41], and in mice, genetic mutations can alter fetoplacental

vascularity [10, 5, 22]. Understanding the mechanisms controlling the growth and structure of the arterial tree is important given its critical role in distributing fetoplacental blood flow throughout the exchange region, and its undoubtedly significant role in determining the total vascular resistance of the bed, a critical factor in determining flow. The latter conclusion is based on our current understanding of the distribution of vascular resistance in systemic vascular beds, where resistance in capillaries and veins is relatively low, and resistance in small arteries and arterioles predominates [31]. Arterial-specific resistance has yet to be determined for the placenta. However, in fetal sheep, the intraplacental arteries, arterioles, capillaries, and venules of the fetoplacental arterial tree in total represent ~55% of resistance across the fetoplacental

circulation with most of the remainder residing in the umbilical artery itself [2]. Our click here limited understanding of the factors determining the structure of arterial trees is due at least in part to the difficulty of visualizing, quantifying, and analyzing their structure, and statistically evaluating how the structure is altered by environment or genetics. Micro-CT imaging has enabled the generation of 3D data sets that Bumetanide capture the morphology and topology of arterial trees with high resolution [36, 7, 24] (Figure 1). Automated segmentation techniques have been used to analyze these datasets generating reconstructed images and quantitative parameters [35]. Indeed,

detailed vascular analysis of other organs including the brain [12], lung [43], kidney [40, 32], liver [8, 19], and of the placenta [5, 36, 35, 11] have been undertaken. Thus, we are now at a stage where the effect of genes and environmental factors on the structure of the fetoplacental arterial tree can be quantitatively evaluated. In this review, we describe the strengths and weaknesses of micro-CT quantitation of the fetoplacental arterial tree in mice, describe recent insights into factors affecting the fetoplacental arterial microcirculation that were made possible with this technique, and will highlight important areas for future investigation. Micro-CT is a high resolution X-ray imaging modality that can provide 3D, quantitative information on the vascular tree [7, 26].

The gene for TNF is polymorphic. Several TNF promoter SNPs have been reported to be associated with disease in humans. DNA sequence variations modifying transcriptional regulation of gene [154] play important role in many complex diseases. The first 200 bp of the

promoter are highly conserved across a range of species, with the murine, bovine and porcine promoters showing approximately 80% homology with the human promoter; while further upstream, there is far less conservation Hydroxychloroquine between species. It has been reported that TNF rs1800630 polymorphism was associated with reduced level of serum TNF-α, because this polymorphism is strongly influence the binding of nuclear proteins [158]. In gene expression, the multiple TFs first assemble at the promoter site and the recruit RNA polymerase. These TFs bind to their cognate binding sites in the promoter region. The presence of polymorphism in regulatory region affects the interaction of TFs with transcription factor–binding site (TFBS), influencing

the expression of gene and thus susceptibility/resistance to disease. We have also predicted several SNPs in the promoter of TNF-alpha, computationally, which lies in TFBS of several TFs in upstream region of TNF-alpha (Table 4). Therefore, we hypothesized that predicted SNPs interfere with gene regulation NVP-BKM120 solubility dmso and will increase the susceptibility to disease. Tumour necrosis factor promoter polymorphism and susceptibility to falciparum malarial infection and pulmonary tuberculosis have been carried out in Indian population. In malaria, TNF-α rs1799964 C and rs1800630 A-alleles as well as homozygotes for the TNF enhancer haplotype CACGG correlated with enhanced plasma TNF levels in both patients and controls. Significantly, higher TNF levels were observed in patients with severe malaria. In tuberculosis, no significant

differences of the allele frequencies between the patients with tuberculosis and controls have been reported but a significant difference in the serum TNF-α level in the patients and the controls has been found. Two TNF polymorphisms rs1800629 and rs361525 show association in most of the diseases (if MTMR9 any association found). Probably, these polymorphisms affect the transcription of gene. Polymorphisms of TNF are likely to contribute to disease, the complex pattern of associations that has been revealed could also be attributable to LD with another susceptibility locus in the vicinity of the gene. By examining LD patterns, we determined that the effect of TNF is independent of the known HLA–A and HLA–DRB1 associations (Fig. 4). The chromosomal region surrounding TNF, however, is abundant in genes of immunologic relevance. To identify true susceptibility genes, the genetic variation of the region must be studied, and extended haplotypes must be constructed and analysed.

Activity of Na+/K+-ATPase, selleckchem measured by 86rubidium (86Rb) influx, revealed a 16·2% ± 13·1% (P < 0·01) decrease of 86Rb-influx upon LPS stimulation (Fig. 2b). In LPS-stimulated AECII co-exposed to sevoflurane 86Rb-influx reached values comparable to the control group (P < 0·01). No difference in 22Na-influx was observed in all four groups (Fig. 3a). Na+/K+-ATPase

activity in mAEC was increased by 23·7% ± 24·5% in the LPS group, 26·1% ± 38·6% in the sevo/LPS group (both P < 0·05). Sevoflurane did not have a significant impact on LPS-injured mAEC (Fig. 3b). mRNA of α-ENaC was decreased by 58% ± 26·9% in the propofol/LPS compared to the propofol/PBS group (P < 0·05) (Fig. 4a). Sevoflurane co-conditioning did not impact upon the expression of α-ENaC mRNA. γ-ENaC mRNA was down-regulated in both LPS groups compared to propofol/PBS: it decreased by 81·7% ± 12·9% (P < 0·01) in the propofol/LPS and 71·7% ± 17·3% selleck (P < 0·01) in the sevoflurane/LPS

group (Fig. 4b), with no intergroup difference. Despite an increased expression of α1-Na+/K+-ATPase mRNA in LPS-treated compared to control animals (increase of 46·5% ± 114·6 in the propofol/LPS and 99·4% ± 81·4 in the propofol/LPS group), values between all groups did not differ significantly (Fig. 4c). While LPS application impaired oxygenation in the propofol group, oxygenation could be maintained in sevoflurane/LPS-treated animals comparable to propofol/PBS (Fig. 5): at 6 h, propofol/LPS animals presented with an oxygenation index of 298 ± 180 mmHg compared to 6 h sevoflurane/LPS animals with 466 ± 50 mmHg (P < 0·05). At 8 h the difference even increased, with 198 ± 142 mmHg selleck chemicals llc in propofol/LPS animals to 454 ± 25 mmHg in LPS animals with

sevoflurane application (P < 0·001). A 27·7% ± 21·2% higher wet/dry ratio in animals treated with propofol/LPS compared to sevoflurane/LPS was observed (P < 0·05) (Fig. 6a). Sevo/LPS animals treated with amiloride presented similar wet/dry ratios to the group without amiloride application (Fig. 6b). With the current data, two main results can be summarized: first, sevoflurane has a stimulating effect on the pump function of sodium channels in LPS-injured AECII in vitro. However, no such impact was observed in a mixed culture of types I and II AEC (mAEC); rather, this cell composition reflected an in-vivo situation with predominantly type I cells in the lung. In-vivo data underline these findings, demonstrating that the presence of sevoflurane does not influence oedema resolution. Secondly, sevoflurane has a positive impact upon the course of LPS-induced injury in vivo. Animals anaesthetized with sevoflurane presented with better oxygenation. Transepithelial sodium transport plays an important role in fluid clearance in normal and injured alveoli. α-ENaC thereby seems to be crucial, as α-ENaC-deficient mice died shortly after birth due to lung oedema even without pulmonary inflammation [43].

31–33 Interestingly, ICCs in the lamina propria respond to ATP but not to muscarinic agonist carbachol, selleck chemical while ICCs in the detrusor respond to carbachol via M3 receptor, indicating a parasympathetic control of ICCs in the detrusor.34 This implies the two types of ICCs have different functional

roles in the bladder physiology. Spontaneous electrical activity and Ca2+-transients in the ICCs and close structural connections with nerves and SMCs26,35 have suggested that the ICCs may be pacemaking cells of SCs in the bladder. Indeed, the c-Kit tyrosine kinase inhibitor imatinib mesylate inhibited SCs.36,37 However, the frequency of spontaneous Ca2+-transients differed between the ICCs and neighboring SMCs.38 This evidence contradicts the notion that ICCs in the bladder function as pacemakers. ICCs in the detrusor are positive for cyclooxygenase buy Roxadustat related to prostaglandins synthesis,39,40 and a recent study showed that ICCs in the detrusor have numerous vesicles, indicating a secretory function.41 Therefore, ICCs

may control the SMC activity by releasing a modulator. This is an attractive hypothesis. There are at least three factors that may contribute to changes in the SCs due to SCI or BOO: myogenic alterations, local mediators in the detrusor and urotheliogenic modulation (Table 1). SMCs have spontaneous electrical and contractile activity. However, electrical coupling is normally limited to some neighboring cells, and action potentials may spread through gap junctional intercellular communication.42 In BOO, cell-to-cell communication between primary cultured SMCs of bladders stained with a fluorescent dye was enhanced in SMCs from rats with BOO compared with those from control rats.43 This enhancement was inhibited by a gap-junction inhibitor. Enhanced cell-to-cell communication may, therefore, contribute to the enhanced SCs associated with BOO. The expression of

connexin 43 gap junctions between SMCs is increased in the human bladder with DO mainly due to SCI.44 This implies that intercellular communication between SMCs is enhanced and may result in enhanced SCs in SCI. Alterations in ion channel activity may be involved in the generation of enhanced SCs Mirabegron in BOO. Downregulation of large and small conductance calcium-activated potassium channels and the TREK-1 potassium channel, and upregulation of calcium-activated chloride channels may cause enhanced SCs.45–47 However, there have been contradictory findings, namely, upregulated expression of potassium channels has also been identified in bladders with BOO.22 The reason for this contradiction is unknown. Further studies of alterations to potassium channels are required. There is an intracellular signal transduction mechanism that can increase the contractile ability of SMCs, that is, calcium sensitization that involves the rhoA/rho-kinase pathway.48 The expression of rhoA and rho-kinase was upregulated in obstructed rat bladders.

brasiliensis-derived antigens. Some CD4 T cells from DO11/4get

mice can still respond to other antigens because allelic exclusion at the TCR α-chain locus is leaky and endogenous TCR α-chains can be expressed in addition to the transgenic α-chain, which leads to development of T cells with two different functional TCRs.25–27 Finally, we used DO11/4get mice on a Rag-deficient background (DO11/4get/Rag−/− mice), which express the transgenic TCR but lack expression of endogenous TCR α-chains so that we could determine whether Th2 cells are induced by cytokine-mediated bystander activation. Very few Th2 cells could be detected in lymph nodes and lungs of naive 4get, DO11/4get and DO11/4get/Rag−/− mice (Fig. 3a). However, on day 9 after infection 4get mice contained about 35% Th2 cells in the lung and about 14% Th2 cells in mesenteric lymph nodes whereas these frequencies selleck inhibitor were reduced to 11% and 5%, respectively, in DO11/4get mice (Fig. 3a,b). The majority of Th2 cells in DO11/4get mice could not be stained with the clonotypic antibody KJ1-26, suggesting that most of these T cells expressed endogenous TCR α-chains, leading to preferential expression of a second TCR (Fig. 3a). The transgenic TCR in DO11/4get mice is composed of Vα5/Vβ8.1 chains. To determine whether endogenous

TCR α-chains are expressed on KJ1-26+ cells we stained peripheral blood samples from DO11/4get mice with antibodies against two different endogenous TCR α-chains. Among all KJ1-26hi cells, about 4·4% co-expressed Vα2 and 0·3% co-expressed RG7420 purchase Vα8.3 chains (Fig. 3c). This demonstrates that DO11/4get mice contain a small repertoire of CD4 T cells with TCR specificities that are not restricted to recognition of OVA and some of these cells can mount a Th2 response against N. brasiliensis. Importantly, Th2 cells were completely absent in N. brasiliensis-infected DO11/4get/Rag−/− mice, which demonstrates that the OVA-specific

TCR is not cross-reactive with N. brasiliensis-derived antigens and Th2 cells were not induced by unspecific bystander activation (Fig. 3a,b). To support these findings in another system, we repeated these experiments with Smarta/4get mice, which express a transgenic TCR specific Rolziracetam for lymphocytic choriomeningitis virus (LCMV)GP61–80 peptide in I-Ab. In contrast to DO11/4get mice, N. brasiliensis infection of Smarta/4get mice did not induce Th2 cells (Fig. 4a). This was not because of differences in the genetic background because comparable frequencies of Th2 cells were observed in normal 4get mice on C57BL/6 or BALB/c background (compare Figs 3a and 4a). However, co-expression of three different endogenous TCR α-chains (Vα3.2, Vα8.3 and Vα11) together with the transgenic Vα2 chain was not observed in Smarta/4get mice (Fig. 4b). This might reflect a more efficient positive selection process in comparison to thymocyte maturation in DO11.