Analysis of the mature protein predicted a molecular weight mass of 13.6 kDa. Positions 31 and 32 of the precursor protein contain the sequence Ala-x-Ala, a motif commonly found preceding the cleavage site 25. The Rv1419p contains a carbohydrate-binding B-chain ricin domain and belongs to the ricin-type β-trefoil family of proteins, which is composed of three homologous subdomains as well as the presence

of a Q-W pattern 26. B-chain ricin domains have been demonstrated to bind cell surface glycolipids and glycoproteins bearing β-1,4-linked galactose and mannose moieties 27. In addition, database searching Selleckchem Crizotinib has shown that the Rv1419 ORF displays 100% identity with its homologue from the clinical strain Mtb CDC1551 (GenBank accession number: AE000516.2) as well as M. bovis BCG (GenBank accession number: AM408590.1) and 78% identity to M. marinum (GenBank accession number: CP000854.1) as well https://www.selleckchem.com/Wnt.html as M. ulcerans (Genbank accession number: CP000325.1) homologous gene (Table 1). These data suggest the existence of a previously uncharacterized secreted carbohydrate-binding protein from Mtb and related sequences in other mycobacteria. To further study possible functions of Rv1419 gene product, we have produced a recombinant protein as described in the Materials and methods section. A DNA fragment

of 496 bp was obtained (Fig. 1B), purified, and cloned into the vector pMOSBlue. Sequencing procedure confirmed that cloning and amplification experiments generated an unaltered Rv1419 sequence (data not shown). The fragment was then inserted in-frame with the start codon present at NdeI cleavage site into the plasmid pET15b enabling full production of Rv1419-gene product Erastin using Escherichia coli. Figure 1C shows a typical SDS-PAGE experiment of the obtained recombinant Rv1419p demonstrating a single band with molecular weight of ∼17 kDa. Additionally, we have confirmed that Rv1419p possesses lectin activity based on classical erythrocyte agglutination assays (Fig. 1D). Following bidimensional gel analysis and mass spectrometry

of CFP from Mtb H37Rv, Malen et al. have recently detected a spot corresponding to the Rv1419 gene product 13. To further investigate whether Rv1419p is secreted and/or expressed in other Mtb compartments, we have generated a mAb (clone 276.B7/IgG1Kappa) against this protein. Figure 2A reveals a single ∼13 kDa band in CFP preparations from Mtb H37Rv, but not in the CFP fractions obtained from the non-tuberculous mycobacteria species M. avium, M. kansasii, M. fortuitum. Compared with the Mtb CFP, the whole cell lysate, cell wall, or membrane preparations presented lower amounts of a similar ∼13 kDa band following incubation with the mAb (Fig. 2B). In contrast, as previously demonstrated 28, high levels of the 19 kDa lipoprotein corresponding band from Mtb H37Rv were observed in the studied fractions incubated with an anti-19 kDa lipoprotein mAb (Fig. 2B).

Volkman et al. (2) sequenced high-quality draft genomes of three parasite laboratory clones (the reference sequenced as 3D7, HB3 and Dd2) isolated from different parts of

the world. Their work alone identified 26845 single-nucleotide polymorphisms (SNPs) at a frequency of one SNP every 780 bases between the three clones and an additional 37 039 insertion–deletions (indels) between 3D7 and HB3. They further extended their genotyping to 12 P. falciparum strains and 20 genomic regions from 54 worldwide P. falciparum isolates. Results were consistent with initial genetic diversity studies that Venetoclax were performed using whole-genome microarray analysis (5). All together, they identified more than 46937 SNPs (one every 446 bases in average) across the whole genome. High levels of SNPs were detected in genes involved in antigenic variation as well as genes involved in drug resistance. These data were further confirmed by the survey of approximately 60% MLN0128 research buy of P. falciparum predicted genes (3)

and a shotgun sequencing strategy of a Ghanaian clinical isolate (4). Taken together, these reports identified a high number of rare SNP variants and suggested that most SNPs have yet to be discovered. As a whole, these results underscore the importance of creating comprehensive maps of genetic diversity in P. falciparum field isolates. These SNPs are strongly suspected to be markers for various phenotypic traits such as virulence or resistance to drugs.

Recent advances in next-generation sequencing (NGS) technologies are enabling fast and affordable production of large amounts of genome sequence information. These technologies are already opening new perspectives of functional genomics in the field of primary, applied and clinical malaria research. After 30 years of dominance of first-generation ‘Sanger’ dideoxy sequencing, the past 5 years Farnesyltransferase have seen the explosion of NGS methods. Next-generation sequencing has transformed the field of whole-genome sequencing and analysis. Unlike Sanger sequencing, NGS avoids the need for bacterial cloning and therefore bypasses associated biases. For example, AT- or GC-rich regions are often toxic to bacteria and difficult to reliably read with cloning-based sequencing. This issue is of major importance in the case of the P. falciparum’s extremely AT-rich genome. The major leap forward from NGS is the ability to produce an enormous amount of data within small volumes; a tremendous number of DNA fragments, up to 2 billion short reads per instrument run, can be sequenced in parallel. Three main NGS platforms have been commercialized over the past 5 years: the Roche 454 (Roche Life Sciences, Branford, CT, USA), the Applied Biosystems SOLiD (Applied Biosystems , Carlsbad, CA, USA) and finally the Illumina® (formally known as Solexa) Genome Analyzer and Hi-Seq platforms.

We conclude that modification of antigen with either 3-sulfo-LewisA or tri-GlcNAc enhances cross-presentation and permits Th1 skewing, through specific targeting of the MR, which may be beneficial for DC-based vaccination strategies to treat cancer. Activation of antigen-specific cytotoxic T cells is crucial for the induction of adequate

anti-tumor immunity. Since most tumor cells are poorly immunogenic, optimal presentation BGB324 solubility dmso of tumor-derived antigens in MHC class I molecules on the surface of antigen presenting cells is required. An important mechanism that allows DCs to present exogenous antigens, such as tumor-derived antigens, in MHC class I molecules is cross-presentation 1. At tumor lesions, multiple factors and cells are present that prevent the proper activation of DCs that enter the lesion to sample for antigens 2, 3. Consequently, these DCs will not be able to properly activate antigen-specific CD8+ T cells in the tumor-draining LN. To obtain therapeutic anti-tumor immunity powerful vaccination protocols are required. Current strategies focus

either on ex vivo loading of autologous DCs as well as specifically targeting of antigens to DCs in vivo. These new therapies may be combined with a Treg depletion regimen, as these cells have been shown to block anti-tumor immune responses 3–6. As a classical C-type lectin this website receptor (CLR), the mannose receptor (MR) binds carbohydrate structures such as mannose, fucose and N-acetylglucosamine (GlcNAc) in a calcium-dependent manner 7, 8. Besides these carbohydrate structures, the MR has recently also been reported to bind sulfated sugars, such as sulfated oligosaccharides of the blood group antigens LewisA (LeA) and LewisX (LeX) 8–10. Binding of these types of ligands occurs via the cysteine-rich (CR) region of the MR and in a calcium-independent manner 8. The MR has been proposed to mediate antigen uptake and presentation by DCs based on the finding that mannosylated proteins are presented Dichloromethane dehalogenase more efficiently than non-mannosylated proteins 11, 12. Fusion of an MR-specific monoclonal antibody to tumor antigens enhanced MHC class I-restricted T-cell

responses 13. Additionally, the glycoprotein ovalbumin (OVA), which contains mannose residues, was reported to be endocytosed through the MR, upon which the antigen was transferred to early endosomes, resulting in strong cross-presentation 14, 15. By contrast MR-mediated uptake of OVA did not induce CD4+T-cell responses. Processing of native glycosylated OVA in the early endosomes occurs in a TAP-dependent manner. Transport of TAP from ER to the endosomes is mostly, but not entirely, dependent on toll-like receptor-4 (TLR4)/MyD88 signaling 15. Although these studies report that the MR is an endocytic receptor for mannosylated OVA, in the human setting mannose may simultaneously target other CLR such as DC-SIGN, which shares specificity for mannose 16.

5a). SB203580 had no effect on MCP-1 secretion by human monocytes (Fig. 5a). Surprisingly, rottlerin enhanced

the effect of co-stimulation with PAR2-cAP and IFN-γ on MCP-1 secretion by monocytes (Fig. 5a) and also enhanced PAR2-cAP-induced MCP-1 release when PAR2 agonist was used alone (Fig. 5b). However, rottlerin did not affect MCP-1 levels in IFN-γ stimulated cells (data not shown). We were also interested in whether rottlerin alone might affect MCP-1 secretion by human monocytes and found that it did increase secretion (Fig. 5c). SB203580 and JAK inhibitor each did not affect MCP-1 secretion triggered GS-1101 concentration by PAR2-cAP (Fig. 5b). LY294002 slightly reduced the effect of PAR2-cAP stimulation on MCP-1 secretion by human monocytes (the level of MCP-1 secretion after PAR2-cAP application was 271 ± 60 pg/ml and if LY294002 was also added, the level of MCP-1 was 154 ± 72 pg/ml) (Fig. 5b). In all cases, treatment of monocytes with DMSO did not affect MCP-1 secretion (Fig. 5a–c). The most important finding of our study is that PAR2 activation enhances phagocytic activity against Gram-positive (S. aureus) bacteria and the killing of Gram-negative Maraviroc in vivo (E. coli) bacteria

by human leucocytes. The magnitude of the bactericidal effect induced by PAR2 agonist was similar to that induced by IFN-γ (Figs 1 and 2; see supplementary material, Fig. S1). Since PAR2 agonist can synergize with IFN-γ in enhancing anti-viral responses,8,9 we PD184352 (CI-1040) investigated whether co-application of PAR2-cAP and IFN-γ led to stronger anti-bacterial responses of innate immune cells, but found that the response was no greater than when each compound was used alone (Figs 1 and 2; Fig. S1). In addition, PAR2 agonist stimulation also failed to enhance LPS-stimulated phagocytic activity of neutrophils and monocytes (see supplementary material, Fig. S2). Hence, PAR2 stimulation might trigger additional mechanisms that enhance the phagocytic activity of innate immune cells, and these mechanisms do not synergize with IFN-γ or LPS-triggered ones. Unfortunately, it

remains problematic to investigate whether the classic PAR2 activators trypsin and tryptase can affect phagocytic and bacteria-killing activity of human innate immune cells. Trypsin and tryptase are known to induce PAR-independent effects.5,6 These effects could confound the data obtained using these enzymes as PAR2 agonists. Cytokines and chemokines influence the recruitment of phagocytes to the site of pathogen infection. The PAR2 agonists reportedly affect the secretion of IFN-inducible protein-10, IL-8, IL-6 and IL-1β by human neutrophils, monocytes and endothelial cells.8,10,27 Among chemokines, MCP-1 appears to play a distinct role linking neutrophils and monocytes during time-delayed inflammatory response, and helping to resolve inflammation via activation of efferocytosis.14 In addition, IFN-γ reportedly enhances time-delayed MCP-1 secretion by human neutrophils.

We describe an unusual case of giant cell angiitis beginning as a hemorrhagic tumoral-like lesion. The results of the histological and ultrastructural analysis have also been reported. Our case illustrates that giant cell angiitis should be considered as a cause of intracerebral hemorrhage, particularly when associated with a relapsing and remitting disease of the CNS. “
“M. Fèvre-Montange,

A. Vasiljevic, D. Frappaz, J. Champier, A. Szathmari, M.-H. Aubriot Lorton, F. Chapon, A. Coulon, I. Quintin Roué, M.-B. Delisle, D. Figarella-Branger, A. Laquerrière, C. Miquel, J.-F. Michiels, M. Péoch, M. Polivka, F. Fauchon and A. Jouvet (2012) Neuropathology and Applied Neurobiology38, 87–94 Utility of Ki67 immunostaining in the grading of pineal parenchymal tumours: a multicentre study Aims: Pineal

parenchymal tumours (PPTs) are rare neoplasms that are divided into R428 datasheet pineocytoma (PC), pineoblastoma (PB) and PPT of intermediate differentiation (PPTID). Factors affecting the survival of patients with PPTs are morphological subtype and histological grading according Rapamycin to mitotic index and neurofilament immunostaining. Grading criteria to distinguish PPTIDs are difficult to define, particularly when using small specimens. The Ki67 labelling index (LI) might be helpful in distinguishing between grade II and III PPTIDs. Our study was performed to assess the predictive value of the Ki67 LI in a large cooperative series of PPTs and to evaluate

whether inclusion of this data would improve and refine the World Health Organization classification. Methods: A retrospective analysis of 33 PPTs was performed. The histological features of the tumours were reviewed and Ki67 LI scoring was evaluated by immunohistochemistry. Data were correlated with the patients’ survival. Results: The mean Ki67 LI was significantly different for tumour grades (0 in PC, 5.2 ± 0.4 in PPTID grade II, 11.2 ± 2.0 in PPTID grade III, 36.4 ± 6.2 in PB; P < 0.0001). However, there was no statistically significant difference in either overall or disease-free survival evaluated by the Kaplan–Meier method for patients with different grade tumours or Ki67 LI, possibly due to the different clinical Myosin management of patients in different centres. Conclusions: The Ki67 LI may be a useful additional tool for grading PPTs, more particularly in small tumour samples. “
“We report an autopsy case of a 75-year-old Japanese woman with motor neuron disease (MND) showing numerous neuronal and glial inclusions immunostained with anti-fused in sarcoma (FUS) antibody. At 73 years, she received a diagnosis of MND and died of respiratory insufficiency 2 years later. No mutation was found in all exons of the FUS gene. Neuropathological examination revealed a reduced number of anterior horn cells and degeneration of the pyramidal tracts.

To this end, we used a transgenic ERE-luciferase (Luc) reporter mouse model [13]. One recent 10-week Phase II clinical trial investigated an agonist of ERα (Org 37663) in postmenopausal RA, and found no clinical benefit despite induction of oestrogenic responses in several organ systems [14]. In another recent

12-week Phase II trial an agonist of ERβ (ERB-041) was investigated, and similar results were found [15]. One explanation may be that the duration of the trials was not long enough to induce clinical benefit, as a previous trial with HRT showed benefit only after 2 years. As animal studies with both compounds had shown anti-arthritic properties, it is important to investigate selleck products further the mechanisms for these effects, and to evaluate whether there is a difference between different species [16,17]. Indeed, we have shown previously that stimulation of ERα ameliorated CIA in mice, whereas an agonist of ERβ did not, while the specific ERβ agonist ERB-041 improved arthritis in rats [18]. Based on the current study, we conclude that neither the SERM raloxifene nor oestradiol had any effect on the induction phase of CIA. Oestradiol, but not raloxifene, modified the effector phase of the disease in CAIA. Raloxifene activated the X-396 classical signalling pathway to promote gene transcription, although not to the same extent as oestradiol. However, both compounds displayed potent anti-osteoporotic properties in lipopolysaccharide (LPS)-induced bone

loss seen in CAIA. The ethical committee for animal experiments at Gothenburg University approved this study. Female DBA/1 mice were purchased from Taconic M&B A/S (Ry, Denmark). Male transgenic 3 × ERE-TAT-Luc (ERE-luciferase) mice, on a mixed CBA × C56Bl/6 J background, were generated as described previously [13]. Mice were electronically tagged and kept, five to 10 animals per cage, under standard environmental conditions, and fed standard laboratory chow and tap water ad libitum. OVX and sham operations were performed at 10 weeks of age. Ovaries were removed through a midline incision of the skin, and flank incisions of the peritoneum. The skin incision was then closed with metallic clips. Sham-operated

animals had their ovaries exposed but not removed. Orchiectomy was performed at 20 weeks of age. Testes were removed through an incision of the scrotum, and the incision Tau-protein kinase was closed with a metallic clip. Surgery was performed after ketamine (PfizerAB, Täby, Sweden) and medetomidin (OrionPharma, Espoo, Finland) anaesthesia. Carprofen (OrionPharma) was used postoperatively as a painkiller. Induction phase.  CIA was induced 2 weeks after OVX in female DBA/1 mice. Treatment with raloxifene, oestradiol or vehicle 5 days per week was started 2 days prior to immunization and continued for 12 days. A booster injection of collagen II with incomplete Freund’s adjuvant was given 3 weeks after immunization, and arthritic score and severity were monitored. Mice were terminated 2 weeks later. Effector phase.

Whilst these guidelines are targeted towards care at the terminal stage of disease, they do include a useful analgesic ladder. The guidelines in general are produced as easy to follow flow charts and cover symptoms and signs including constipation, pruritis, pain and dyspnoea. Some guidelines such as those covering fever, would not be

appropriate in most RSC patients as the only recommendation is for the use of paracetamol. In an actively managed RSC patient not yet approaching EOL, antibiotics are more likely to be the management choice. The St George’s Hospital web-site[3] also includes a section on palliative care drug guidelines. This has been selleck chemical adapted from the Yorkshire Palliative Medicine Guidelines (2006) and gives comprehensive information about drug usage including dose and timing adjustments, elimination and other helpful

comments to guide the prescriber. There is also a useful powerpoint presentation from Dr F Brennan covering symptoms and the evidence for various treatments. In particular, this is helpful for conditions such as Restless Legs Syndrome and pruritis which are often very difficult to manage. In North America, the Mid-Atlantic Renal Coalition (MARC) and Kidney End of Life Coalition have developed a clinical algorithm to treat pain in dialysis patients. Whilst these clinical guidelines were developed to aid management of pain specifically in dialysis patients, they provide a useful review Tanespimycin research buy of suitable analgesics and an analgesic ladder specifically adapted for patients with renal failure. Nociceptive and neuropathic pain is covered as well as the management of analgesia-associated side effects. Further dosage adjustments may be necessary for certain medications (e.g. Gabapentin) in patients choosing not to dialyse.

see more Some guidelines deal with how to manage discussions around the question of dialysing, others concern themselves with what is necessary for adequate service provision. In Australia and New Zealand, the CARI Guidelines include two sections of note – ‘Ethical Considerations’ and ‘Quality of Life’. The suggestions in the section ‘Ethical Considerations’, dealing with acceptance onto dialysis, are based on level III and IV evidence and are not protocols for management of people choosing a supportive care pathway. This paper does discuss the concept of ‘benefit’ to the patient. Trials of dialysis are also discussed where there is uncertainty about potential benefit from dialysis. It does not discuss the potential disadvantages of such a trial and what evidence may be available to support this approach. The section on ‘Quality of Life’ again deals with recommendations at a level III or IV only – no recommendations based on higher level evidence are possible.

Since there is a lack of data, we aimed to define the expression pattern and cellular source of TNFRSF9 in human gliomas. find more We investigated TNFRSF9 expression in normal human CNS tissue and glioma

specimens using immunohistochemistry, immunofluorescence and western blotting techniques. Our results show that TNFRSF9 is considerably upregulated in human gliomas when compared to normal brain tissue. In addition, our data provides evidence for an immune cell-independent de novo expression pattern of TNFRSF9 in mainly non-neoplastic reactive astrocytes and excludes classic immunological cell types, namely lymphocytes and microglia as the source of TNFRSF9. Moreover, TNFRSF9 is predominantly expressed in a perivascular and peri-tumoral distribution with significantly higher expression in IDH1 mutant gliomas. Our findings provide a novel, TNFRSF9-positive, reactive astrocytic phenotype and challenge the therapeutic suitability of TNFRSF9 as a promising target for human gliomas. “
“Uranium olfactory uptake after intranasal exposure raises some concerns for people potentially exposed to airborne radionuclide contamination as the brain could be a direct target for these contaminants. A model of nasal instillation was used to elucidate the transport

mechanisms of uranium to the brain and to map its localization. Increasing concentrations of depleted uranium containing solutions were instilled in the nasal cavity of adult male rats. Uranium concentrations Venetoclax price were measured using inductively coupled plasma-mass spectrometry (ICP-MS) 4 h after instillation. Olfactory neuroepithelium cytoarchitecture was

studied using immunohistochemistry experiments. Secondary ion mass spectrometry (SIMS) microscopy Astemizole was performed to localize uranium in the olfactory system. ICP-MS analyses showed a frontal accumulation of uranium in the olfactory bulbs associated with a smaller increase in more caudal brain regions (frontal cortex, hippocampus and cerebellum). Uranium concentrations in the olfactory bulbs do not reach a saturation point. Olfactory nerve bundle integrity is not affected by uranium as revealed by immunohistochemistry. SIMS microscopy allowed us to show that uranium localization is mainly restricted to the olfactory neuroepithelium and around olfactory nerve bundles. It is subsequently detected in the olfactory nerve layer of the olfactory bulb. These results suggest the existence of a transcellular passage from the mucosa to the perineural space around axon bundles. Uranium bypasses the blood brain barrier and is conveyed to the brain via the cerebrospinal fluid along the olfactory nerve. Future studies might need to integrate this new contamination route to assess uranium neurotoxicity after nasal exposure. “
“We present a rare case of primary T-cell lymphoblastic lymphoma of the pituitary gland. A 58-year-old woman presented with headaches, right-sided ptosis and cranial nerve III palsy.

2a). The B220+ CD43− fraction can be further subdivided based on surface IgM and IgD expression into pre-B (IgM− IgD−), immature

(IgM+ IgD−) or mature (IgM+ IgD+) B cells29 (Fig. 2a). We found that WT and dnRAG1 mice exhibited Dinaciclib molecular weight a similar percentage and absolute number of B220+ CD43+ B cells, but the more mature B220+ CD43− B-cell subset was slightly lower in dnRAG1 mice compared with WT mice because of a significant reduction of mature B cells (Fig. 2a,b; see Supplementary material, Table S2). Taken together, these data suggest that dnRAG1 expression impairs B-cell development in the bone marrow at the immature-to-mature B-cell transition. Upon reaching the immature stage, B cells migrate to the spleen to complete their maturation, progressing through phenotypically and functionally distinct transitional stages during this process.30,31 Splenic B220hi B cells can be initially segregated based on the differential expression of AA4.1 (CD93) into transitional (B220hi AA4.1+) and mature (B220hi AA4.1−) subsets. Transitional cells can be further classified into subsets based on the CB-839 concentration differential expression of surface IgM and CD23.32 T1 B cells (IgMhi CD23lo) are considered as immature B cells that have recently emigrated from

the bone marrow, which can differentiate into T2 B cells (IgMhi CD23hi).32 A third transitional B-cell subset, T3 (IgMlo CD23+), is thought to consist of immature B cells that have been rendered anergic by encounter with self-antigen.31,33 The mature B-cell population can be further subdivided by the differential expression of CD21 and CD23

into follicular (CD21int CD23−) and marginal zone (MZ; CD21hi CD23+) B-cell subsets.31 Consistent with observations in the bone marrow, dnRAG1 mice exhibit a significant reduction in the number of splenic transitional (B220hi AA4.1+) B cells compared with WT mice, because of a significant loss of cells in the T2 and T3 subsets (Fig. 2a,b; see Supplementary material, Table S2). In dnRAG1 mice, the mature B220hi AA4.1−subset is also significantly reduced relative to WT mice, with most of the difference attributed Adenosine triphosphate to a significant decrease in follicular B cells, but not MZ B cells (Fig. 2a,b). To explain the lack of an apparent defect in early B-cell maturation and in T-cell development in dnRAG1 mice, we used qPCR to detect total RAG1 transcript in various tissues and compare the relative abundance of RAG1 transcript between normal and dnRAG1 mice after normalizing to an internal calibrator (β-actin). From these experiments, we found that splenic RAG1 transcript levels are about 120-fold higher in dnRAG1 mice compared with normal littermates, but little difference was observed in thymus, bone marrow, lymph node, or liver (Fig. 3a,b).

In this study, we investigated the role of SQSTM1 in host responses to Legionella pneumophila, an intra-cellular pathogen that infects macrophages, in both an SQSTM1-deficient

(SQSTM1−/−) mouse model and macrophages from these mice. Compared with wild-type (WT) macrophages, the production and secretion of the proinflammatory cytokine IL-1β was click here significantly enhanced in SQSTM1−/− macrophages after infection with L. pneumophila. Inflammasome activity, indicated by the level of IL-18 and caspase-1 activity, was also elevated in SQSTM1−/− macrophages after infection with L. pneumophila. SQSTM1 may interact with nucleotide-binding oligomerization domain-like receptor family, caspase AZD5363 in vivo recruitment domain-containing 4 and nucleotide-binding oligomerization domain like receptor family, pyrin domain containing 3 proteins to inhibit their self-dimerization. Acute pulmonary inflammation induced by L. pneumophila and silica was enhanced in SQSTM1−/− mice with an increase in IL-1β levels in the bronchoalveolar lavage fluids. These findings suggest

that SQSTM1 is a negative regulator of acute pulmonary inflammation, possibly by regulating inflammasome activity and subsequent proinflammatory cytokine production. “
“Common variable immunodeficiency disorders (CVID) are a group of heterogeneous check details conditions that

have in common primary failure of B cell function, although numerous T cell abnormalities have been described, including reduced proliferative response and reduced regulatory T cells. This study compared the T cell phenotype of CVID patients subdivided into clinical phenotypes as well as patients with partial antibody deficiencies [immunoglobulin (Ig)G subclass deficiency and selective IgA deficiency], X-linked agammaglobulinaemia (XLA) and healthy and disease controls. Absolute numbers of T cell subpopulations were measured by four-colour flow cytometry: naive T cells, central and effector memory and terminally differentiated (TEM) T cells, using CD45RA and CCR7 expression. Early, intermediate and late differentiation status of T cells was measured by CD27/CD28 expression. Putative follicular T cells, recent thymic emigrants and regulatory T cells were also assessed. Significant reduction in naive CD4 T cells, with reduced total CD4 and recent thymic emigrant numbers, was observed in CVID patients, most pronounced in those with autoimmune cytopenias or polyclonal lymphoproliferation. These findings suggest a lack of replenishment by new thymically derived cells. CD8 naive T cells were reduced in CVID patients, most significantly in the autoimmune cytopenia subgroup.