27 The reduced plasma volume may be explained by the capillary leak syndrome and volume redistribution into the extracellular space, as there is no reduction in extracellular fluid volume.28 Therefore, the elevation in blood pressure may be more closely related to endothelial dysfunction and later, vasoconstriction rather than any direct effect of the RAAS.11 Alternative locally vasoactive compounds such as endothelin, nitric oxide inhibition, oxidative stress or cytokines have been implicated as vasoconstrictors in preeclampsia but LY2109761 ic50 are not proven.29 The use

of antioxidants in humans has not been shown to treat or prevent preeclampsia.30 Interest in the endothelial cell integrity provided by angiogenic factor vascular VEGF (vascular endothelial growth factor) in pregnancy and its potential role in preeclampsia are not new.31,32 There was a resurgence in interest in angiogenic molecules after the elegant demonstration of a mechanistic role for the soluble VEGF receptor, soluble fms-like tyrosine kinase-1 (sFLT-1)33 in preeclampsia. The infusion of sFLT-1 in pregnant rodents induced

PDGFR inhibitor hypertension and proteinuria in pregnancy. The pathological feature of renal biopsies in this model is endothelial disruption similar to that seen in human preeclampsia. The same renal lesion, however, was seen in non-pregnant animals, thus providing evidence of direct renal toxic effect of sFLT-1. The specificity of this pathological mechanism in pregnancy rests with the placenta as the likely site of production. Zhao et al. have demonstrated a net increase in sFLT-1 binding in human renal tissue in preeclampsia.34 We and others have shown that the likely source of the sFLT-1 is acute placental ischaemia35,36 and that the effect of ischaemia and sFLT-1 on the renal capillary loops mimic those seen in human de novo disease (Fig. 1). The clinical importance of the increased sFLT-1 in humans

was demonstrated subsequently check details in a longitudinal retrospective study. It was found that the maternal circulating sFLT-1 was significantly increased in women who were to develop preeclampsia later in the pregnancy. The elevation in sFLT-1 was noted about 5–6 weeks prior to the onset of clinically apparent disease.37 The correlation of high sFLT and low binding proteins VEGF and its co-agonist placental growth factor (PlGF) confirm the binding activity of the sFLT-1. The relative reduction in free VEGF (resultant from the increased sFLT-1) has a potentially important role in mediating the renal involvement in preeclampsia as outlined above. Other recently identified toxins in preeclampsia such as soluble endoglin38 do not appear to be a direct glomerular cell toxins,39 at least in animal studies where its effect is most potent in the presence of sFLT-1.

In conclusion, immunization with DNA coding for the TcSPR domain

of TcSP was able to control T. cruzi infection in a mouse model. Therefore, it may be a good candidate for the development of a T. cruzi vaccine. We thank Enrique Martinez de Luna for his technical help, María Guadalupe Aguilar González for DNA sequencing and Patricia Espiritu Gordillo for critically reading the manuscript. BSJ was recipient of a Ph D fellowship from CONACyT, México. This work was supported by grants from CONACyT, México (Grants 47437 and 104119) selleck screening library to JLRE. “
“Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinaemia and recurrent infections. Although the underlying cause is unknown, B cells from most CVID patients fail to differentiate to memory or plasma cells. We investigated if increased apoptosis could influence the fate of B cells. For this purpose we activated purified B lymphocytes of CVID patients with a surrogate T-dependent (anti-CD40) or T-independent [cytosine–phosphate–guanosine oligodeoxynucleotides (CpG-ODN) or anti-immunoglobulin (Ig)M)] stimulus with or without interleukin (IL)-21. We found that CD27+

B cells were more sensitive than CD27– B cells to spontaneous apoptosis and less sensitive to rescue from apoptosis. The addition of IL-21 down-modulated the protective effect check details Cell press of all the stimuli on CD27– B cells and the protective effect of CpG-ODN and anti-IgM on CD27+ B cells. In contrast, IL-21 rescued unstimulated CD27– B cells

and improved the rescue of anti-CD40-stimulated CD27+ B cells. When we compared patients and controls, mainly CD27+ B cells from MB0 patients were less sensitive to rescue from apoptosis than those from MB1 patients and controls after activation, irrespective of the IL-21 effect. Increased apoptosis during an immune response could result in lower levels of immunoglobulin production in these patients. Common variable immunodeficiency (CVID) is the most frequent symptomatic primary humoral immunodeficiency. It includes a heterogeneous group of disorders of unknown aetiology characterized by deficient antibody production, recurrent respiratory infections by encapsulated bacteria, mainly Streptococcus pneumoniae and Haemophilus influenzae, and poor response to vaccination. Patients benefit from immunoglobulin replacement therapy [1-4]. Several genetic mutations and polymorphisms [inducible T cell co-stimulator (ICOS), tumour necrosis factor receptor superfamily, member 13b (TNFRS13B/TACI), CD19, CD20, CD81, B cell-activating factor receptor (BAFF-R) and CD21] have been described in fewer than 10% of CVID patients, while the underlying molecular defect remains unknown for most of them [5-7].

There was an increase in the TNF-α mRNA in the peritoneal cells stimulated with live M. tuberculosis or PPD. In fact, with the live M. tuberculosis stimulation the mRNA expression was sustained beyond 12 h with a further increase at 24 h compared to PPD. Previous reports from our laboratory have shown clearly that after aerosol challenge with virulent M. tuberculosis NVP-AUY922 molecular weight (H37Rv), high levels of TNF-α mRNA expression were evident in the laser capture micro-dissected discrete granulomatous lesions in non-vaccinated, but not in BCG-vaccinated guinea pigs [41,43]. This was also evident when peritoneal, bronchoalveolar lavage cells, spleen or lung digest cells from M.

tuberculosis-infected guinea pigs were restimulated in vitro with PPD [26,42]. However, recent reports have indicated that secretion of TNF-α was dependent on the virulence of M. tuberculosis, as cytokine (TNF-α, IL-6, IL-10) or chemokine [growth-regulated oncogene (GRO)-α] secretion was found to be reduced significantly when human macrophages or dendritic cells were infected with the Beijing strains of M. tuberculosis

compared to the H37Rv strain [44]. Patients infected with Beijing strains were more prone to disease progression, had higher risk of extrapulmonary tuberculosis or were less likely to respond to treatment [45,46]. Previous studies from our laboratory have indicated that in vitro MLN0128 treatment of peritoneal or alveolar macrophages with rgpTNF-α enhanced the TNF-α and IL-12p40 mRNA expression [24,25]. Again, other studies as well as ours have demonstrated Adenosine that TNF-α alone or in combination with rgpIFN-γin vitro-induced expression of MHC class II molecules on macrophages and T cell IL-2 receptors [25,47,48], although TNF-α injection had no effect on MHC class II expression. It is quite possible that TNF-α had an immediate effect on MHC class II expression,

but the effect was not long-lasting until 6 weeks of vaccination. In vitro studies have also shown that TNF-α alone or together with IFN-γ induced an enhanced expression of IL-10 mRNA in peritoneal macrophages from BCG-vaccinated guinea pigs [25]. Injection of TNF-α may be causing intrinsic changes in macrophages in the BCG-vaccinated guinea pigs, as it is known that TNF-α is essential for the differentiation of macrophages into epithelioid cells and in the aggregation of leucocytes into functional granulomas for controlling virulent mycobacterial infection [34]. Clearly, TNF-α injection caused a better clearance of M. bovis BCG in the lymph nodes of these guinea pigs. These results indicate that in vivo administration of rgpTNF-α decreased M. bovis BCG CFUs, increased the PPD skin test response and the proliferative ability of T cells and altered cytokine mRNA expression, thus modulating the function of both T cells and macrophages in guinea pigs after M.

Although transgene/Igh translocations occur frequently to Igh Sγ regions, we cannot detect analogous translocations between the transgene and the endogenous Igh Sμ regions,

indicating that Sμ switch regions may have evolved to prevent trans-switching, perhaps to avoid non-effective switching between Sμ regions on the two Igh homologs. Interchromosomal switch recombination events between the VV29 transgene and the endogenous Igh locus produce Cγ transcripts that are associated with VV29 VDJ segments. We find that these trans-switching Selleck AZD1208 events are AID dependent as VV29:AID−/− mice either do not produce these transgene-derived Cγ transcripts or they produce them at extremely low Ipatasertib levels. As very low levels of transgene-derived Cγ mRNAs have been observed in some VV29:AID−/− mice, a rare AID-independent mechanism for the generation of these Cγ transcripts does exist. Chromosomal translocations in general are dependent on DNA breaks; it seems possible that certain stimuli could cause DNA damage and breaks in an AID-independent manner that leads to these very low levels of transgene switching. For example, immunization with highly immunogenic reagents could cause cellular stress 23–25 that may lead to AID-independent Ig DNA damage. Supporting this notion, it has been reported that immunization of mice with pristane

can result in c-myc/Igh translocations in AID knockout mice 13, 15. The low levels of transgene isotype switching observed in some, but not all, immunized VV29:AID−/− mice indicate that these AID-independent translocations are rare. Furthermore, VV29-Cγ transcripts were not produced in any VV29:AID−/− mice that received one dose of primary immunization (data not shown) or in any VV29:AID−/− in vitro-stimulated B cells, further supporting our

conclusion that the high levels of interchromosomal switch events observed in VV29 mice are dependent on AID. These results are similar to a number of recent studies that clearly demonstrate an important role for AID in Igh chromosomal translocations that involve the c-myc Phosphoglycerate kinase gene 16–20 although the frequency of translocations induced by B-cell stimulation in VV29 mice appears to be much greater. We detected in vitro translocation events in about 3% of the Cγ transcripts (see Materials and methods for the calculations leading to this result). This frequency was based on sequencing of all the PCR-amplified Cγ transcripts to determine the number associated with endogenous VDJ regions. Based on the published sequences for the ten endogenous V genes found among the PCR-amplified Cγ transcripts, the leader primer is 100% homologous to eight of the endogenous V genes, whereas the homologies of the primer to the two remaining endogenous V genes are 96 and 81%.

Methods: Japanese workers in Shanghai under treatment of as least one of diseases of HT, HL,

CKD or DM in outpatient clinic of Huashan Hospital World Wide Medical Center (HWMC) in Shanghai, China who stayed there for more than 6 months were enrolled. Medical Intervention were 1) medical treatment by collaboration Epigenetics Compound Library of monthly visiting doctors from Kitano Hospital (KH) in Osaka, Japan and those of HWMC, 2) coaching of life style by KH nurses resident in Shanghai and 3) attending seasonal health care seminar were performed: Samples of disease status, life style status as behavior modification (BM) score calculated by division of number (N) of BM by N of interview minus 1 and health related QOL score by SF36 were obtained before and after intervention. Results: Within 28 enrolled patients, final 18 (17 male 1 female) were evaluated with full data of SF36. In 16 HT patients, systolic(s) and mean(m) FK506 molecular weight blood pressure (BP) were significantly declined (P < 0.011, P < 0.023, respectively). Significant improvement of role-social QOL was observed (P < 0.046). Correlation between corrected BW and BM score and improvement of health related QOL were observed. Correlation between BM score and physical

and mental QOL improvement was observed. Multiple regression analysis indicated that role-social QOL improvement was independently affected by amelioration of mBP and BW (R-squared: 0.665 and 0.900, P-value: 0.002 and 0.001 respectively). Conclusion: International Joint medical oxyclozanide intervention with intensive coaching of life style has brought about significant elevation of health related QOL of Japanese oversea worker patients

in Shanghai along with correction of BP and especially BW through BM. BUNANI EUNICE, DUMDUM1,2, BUNANI ARCHIE3 1Puerto Community Hospital; 2Cagayan de Oro Medical Center; 3Southwestern University College of Medicine Background: Literatures have emphasized that administration of anticoagulation in dialysis promotes minimal filter clotting and post dialysis bleeding, and improves patient quality of life through prolongation of the vascular access. Objective: This study evaluated the protocol plan designed to deliver both High and Low Molecular Weight Heparins (HMWH, LMWH) as bolus and cath-dwell and develop a relationship between filter clotting, post dialysis bleeding (PDB), blood flow rate (Qb), and activated Partial Thromboplastin Time (aPTT) among hemodialysis (HD) patients. Methods: 208 HD patients were included in an evaluative cross-over design; bolus-LMWH and HMWH as cath-dwell for the first 6 months and vis-à-vis on the next 6 months. Regression and ANOVA were used for analysis with R square as basis related to heparin adjustment and different filters in single-use basis. Results: Results indicated filter clotting among fistula (f = 8, spv = 0.742) and catheter (f = 17, spv = 0.

Macaque and human pDC were shown to have similar TLR expression profiles [25], which is in agreement with the response patterns observed by us. Also TLR-7, TLR-9 and myeloid differentiation primary response gene 88 (MYD88) BYL719 supplier sequences were shown to be identical, whereas there were important differences for interferon regulatory factor 7 (IRF-7) [26]. Other regulatory pathways still need to be explored [37]. Beside TLRs, the C-type lectin receptor (CLR) family plays an important role in the modulation of innate immune responses [38, 39]. Human pDC express the CLRs blood dendritic cell antigen 2 (BDCA2) and dendritic cell immunoreceptor (DCIR) [40]. Cross-linking of DCIR was shown to result in reduced IFN-α induction upon

TLR-9 stimulation [40], and similar inhibitory effects were reported following incubation with the CLR ligand mannan [41]. Interestingly, BDCA2 [our unpublished observation and documented at the NIH non-human primate reagent resource portal (http://nhpreagents.bidmc.harvard.edu/NHP)] and DCIR [42] were shown to be absent on pDC in rhesus macaques. Although not investigated here, a difference in the balance between activating TLRs and inhibitory CLRs could lead to different levels of pDC activation, possibly translating into a difference in cytokine production pattern. A direct comparison between the absolute numbers of pDC, mDC and monocytes in rhesus versus human blood showed that rhesus

macaques had a lower number of pDC, while click here there was no difference in the abundance of the other subsets. The number

of pDC observed, i.e. 3020 ± 1357 cells/μl, is in agreement with several reports on rhesus macaques [16, 18, 24, 25, 43] and considerably less Buspirone HCl than in humans [44]. In contrast, two other studies, where a direct head-to-head comparison was made, showed no difference in pDC number [17, 28], although it must be noted that in those studies the quantification was either performed on PBMC or cynomolgus monkeys imported from Mauritius were used, which have a more limited genetic diversity and might differ from rhesus macaques. The strong IL-12p40 expression in rhesus pDC may have implications for preclinical evaluation of vaccines in this model. For instance, TLR-7/8 containing adjuvants might trigger different responses in macaques than in humans and involve pDC as IL-12 producing cells. Also TLR-9 agonists could be expected to induce an IL-12 response in rhesus macaques, in contrast to humans. Simultaneous production of IFN-α and the inflammatory cytokines TNF-α and T helper type 1 (Th1)-skewing cytokine IL-12 might also lead to a slightly different response pattern to bacterial and viral infection and have consequences for the induction of CD8 responses [45, 46]. We would like to thank Dr F. Verreck for critical reading of the manuscript, Dr S.B. Geutskens for organizing the collection of the human blood samples and H. van Westbroek for preparing the figures.

However it occurs, the kidneys contributed 55–65% of the total clearance of NT-BNP-76 CT99021 mw in a study measuring the fractional excretion of NT-BNP-76 across a number of organs.91 Other studies in a variety of subjects have demonstrated no difference between BNP-32 and NT-BNP-76 in their fractional excretion across a range of kidney function.91–93 These studies included very few patients with GFR below 30 mL/min. Thus, the kidneys are important to the elimination of both forms of BNP but much remains to be determined about the specific mechanisms

in order to explain why elevations in NT-BNP-76 levels are relatively greater than BNP-32 in patients with ESKD. A reference range specific to the level of kidney function would be very useful, but is yet to be developed. This simplistic question summarizes the dilemma of clinicians when dealing with elevated biomarker levels in patients with ESKD. Should my patient with elevated BNP or troponin be referred to the cardiologist for more extensive cardiac evaluation and treatment? Should I accept that many patients with ESKD have such levels and attribute the result to the fact that they are on dialysis? Clearly, the answers to these questions will depend on careful consideration of the clinical context as well as interpretation

of the biomarker. Troponin and BNP are biochemical markers of specific myocardial pathologies selleck products that are very prevalent in patients with ESKD. Furthermore, the association of these markers with increased mortality in asymptomatic patients undergoing Aurora Kinase dialysis is strong, independent of other factors, and has been consistently demonstrated in many different studies. Reduced kidney function probably does affect the level of these biochemical markers but the precise mechanisms for clearance remain to be determined. Reduced kidney function may amplify the biomarker signal from a myocardium under stress.

While disease of both organs contributes to the biochemical abnormality, the strong association with increased mortality and cardiovascular events in otherwise stable asymptomatic dialysis patients suggests that cardiac pathology is the most important contributor to the biomarker elevations. In the general population, risk stratification can be improved after an acute coronary syndrome by combining assessment of troponin, BNP and C-reactive protein.94 A similar ‘biomarker panel’ in asymptomatic dialysis patients was studied but almost all patients had NT-BNP-76 above the cut-off value. Using cTnI, cTnT and C-reactive protein, the risk of death increased as patients with normal cTnI had increased levels of one, then both of the other markers.43 Such an approach has merit because the biomarkers represent different pathophysiological processes. While the data on the prognostic implications of these biochemical markers in patients on dialysis are strong, the data regarding how to use them to guide therapy are weak (Fig. 1).

5). Only the two subjects who received 1010 BMB72 had IgA responses against listeriolysin (data not shown). Responses to influenza nucleoprotein were not detected in these assays. These results were interpreted to represent low level mucosal immune response against the listerial vector only. Serological immune responses RAD001 ic50 were modest at best, with isolated individuals having four-fold or greater titer increases in ELISAs directed against listeriolysin or sonicated listerial antigen (denoted in Table 2 as one or two positive assays). No individual seroconverted to the recombinant nucleoprotein antigen.

Virtually all individuals had relatively high titers directed against recombinant nucleoproteins at baseline, which did not change over time (i.e. ≥1:640). Sera from other species (mouse and rabbit) studied similarly in ELISAs did not have similarly high baseline values, so these were interpreted to selleck chemicals represent bona fide pre-existing immune responses to this influenza protein, rather than inadequate blocking or another technical problem with the assay. A high baseline is not unexpected, as most

subjects had evidence of cellular immunity to influenza A, and it is expected that most healthy young adults would have been exposed to influenza. Grouped by vaccine given, there was no statistically significant increase in IgG mean titers (GMT; pre-immune to peak value) directed against listerial sonicate, listeriolysin or nucleoprotein, as exemplified in Figure 6b (for listeriolysin). Baseline listeriolysin titers were high, which is not unexpected. Antibodies to streptolysins

present in commensal and pathogenic streptococci cross-react with listeriolysin (34). Our volunteers were required to have previously received penicillin Oxalosuccinic acid or ampicillin, commonly administered to treat Group A streptococcal pharyngitis. Overall, mean serum IgA titers did increase modestly when considered as a group for both vaccine organisms (Fig. 6a). All subjects had positive control responses to the lectin PHA (usually TNTC), and all but one to the CEF control pool (subject No. 11 had both robust PHA responses and responses to sonicated listerial antigen, but no apparent response to CEF or influenza nucleoprotein peptides). Most subjects (17/22) had convincing baseline immune responses to at least one of the Influenza A nucleoprotein peptide test pools (tens to many hundreds of spots per million PBMC, see exemplary data in Fig. 7a). About two-thirds of the subjects (14/22) had some baseline responses to the listeriolysin peptide pools, with mean baseline value 21 (range 0–205) SFC/106 PBMC, comparable to others’ published work (35). ELISpot data were analyzed by individual and as a group by vaccine administered, irrespective of dose, as responses overall did not appear dose-related. Values were analyzed as pre-immune vs.

3B), suggesting that the infection could induce an increase in the NADPH oxidase activity in MDSCs. It has been previously

reported that NO and peroxynitrites are crucial mediators of MDSCs-mediated suppression [3]. Therefore, we assessed the expression of iNOS in MDSCs derived from cultures of infected and uninfected splenocytes stimulated with Con A and found a threefold increase in the CD11b+Gr1+iNOS+ cell percentage in infected compared to uninfected mice (Fig. 4A). In addition, we evaluated the tyrosine nitration on the T-cell surface. An increase in TN+CD8+ and TN+CD4+ T cells was detected in infected compared with uninfected mice (Fig. 4B). These results were corroborated www.selleckchem.com/products/CAL-101.html by confocal imaging (Fig. 4C). Cells with these characteristics were also observed in IHL (Fig. 4B). In addition, we tested whether splenic or hepatic MDSCs per se had the ability to produce peroxynitrites. We found

that approximately 70% of infected splenic MDSCs produced this metabolite and about 58% of hepatic MDSCs had the capacity to generate peroxynitrites. In addition, almost GSK-3 inhibitor all MDSCs from uninfected mice stained positive for intracellular nitrotyrosine (Fig. 4D). Taking into account that IL-6 is able to increase MDSCs accumulation [25], we evaluated the number of MDSCs during acute infection in IL-6 deficient mice. A significantly lower number (about threefold) of splenic MDSCs was detected in IL-6 KO compared with wild-type mice (Fig. 5A). Interestingly, IL-6 KO mice showed 100% mortality compared with the wild-type (0%) at 21 dpi (data not shown). Since MDSCs can also produce IL-6 [26], we evaluated IL-6 production at the intracellular level. A higher number of IL-6+ MDSCs was observed in infected versus uninfected mice (Fig. 5B). Furthermore, high levels of IL-6 were detected in culture supernatants

when splenic MDSCs were stimulated with either IL-4 (Th2 cytokine) or IFN-γ (Th1 cytokine) (Fig. 5C). It is known that IL-6 signaling leads to the phosphorylation until of the signal transducer and activator of transcription-3 (STAT3) transcription factor, which plays a critical role in the accumulation of MDSCs [2, 27]. Accordingly, we observed p-STAT3 in 70% of infected splenic MDSCs versus 45% in uninfected cells (Fig. 5D). This finding was supported by confocal microscopy studies (Fig. 5E). To evaluate the importance of MDSCs during parasite infection in BALB/c mice, the drug 5-fluorouracil (5FU) was used at 10 and/or 15 dpi. As has been previously demonstrated, 5FU 50 mg/kg selectively induces splenic MDSCs apoptotic cell death in vitro and in vivo, whereas it has no significant effect on T cells, NK, dendritic, or B cells [28]. Using the 5FU reported dose, a reduction of CD11b+Gr1+ was observed for both treatments with it being highly significant at 15 dpi (Fig. 6A).

tuberculosis infection. Assays showed that

CD4+ T cells produce cytokines IFN-γ, IL-22 and IL-17 following stimulation with immune-dominant peptides of ESAT-6, CFP-10 or with BCG (Fig. 4A). Notably, IFN-γ+CD4+ T cells were more frequent than IL-22+CD4+ or IL-17+CD4+ T cells. In the absence of stimulation, very low frequencies of IFN-γ, IL-22 and IL-17 were produced by CD4+ T cells, which was consistent with the results from ELISA. Statistical analysis confirmed that the immune-dominant peptides of ESAT-6, CFP-10 or BCG induced significantly higher percentages of IFN-γ-, IL-22- and IL-17-expressing CD4+ T cells than medium alone (Fig. 4B, n = 17, P < 0.001 or P < 0.01). However, specific cytokines see more of IFN-γ, IL-22 and IL-17 were mostly produced by distinct populations of CD4+ T cells (Fig. 5A). Statistical analysis showed that the mean distributions of ESAT-6-, CFP-10- or BCG-specific IFN-γ-, IL-22- or IL-17-producing CD4+ T cells were similar (Fig. 5B, n = 17). Very small proportion of IL-22-producing CD4+ T cells also produced IL-17 or IFN-γ after stimulation. Taken together, the IFN-γ-,

IL-22- or IL-17-producing CD4+ T cells in tubercular pleural fluid from patients with TBP were independent T cell subsets. And these T cell subsets might contribute to the protective immune response to M. tuberculosis infection. We investigated the memory phenotype of ESAT-6-, CFP-10- or BCG-specific CD4+ T cells that were able to produce IL-22 or IL-17. As Sirolimus concentration shown in Fig. 6A, most of IL-22-producing

CD4+ T cells were central memory cells with the phenotype of CD45RA−CD62L−CCR7+CD27+. In addition, statistical analysis showed that the distribution of IL-22+CD4+ T cells was nearly consistent following different stimulations (Fig. 6B, n = 4). And the highest percentage of IL-22+CD4+ T cell subsets was CD45RA−CD62L−, CD45RA−CCR7+ and CD45RA−CD27+. The lowest percentage of IL-22+CD4+ T cell subsets was CD45RA+CD62L−, CD45RA+CCR7− and CD45RA+CD27−. We also found that IL-17-producing CD4+ T cells have the same memory phenotype with IL-22 (data not shown). Taken together, IL-22- or IL-17-producing DOK2 CD4+ T cells in pleural fluid were central memory cells and might contribute to long-lasting protection against M. tuberculosis infection in patients with TBP. Most studies on TB have relied on murine models [24], in vitro M. tuberculosis antigen-challenged human bronchoalveolar cells or peripheral blood from patients with TB [25]. But few studies have comprehensively evaluated the role of Th1, Th22 and Th17 cells at the local immune response to M. tuberculosis infection. However, we observed that IFN-γ and IL-22 were elevated in human tubercular pleural effusions. TB antigen-specific production of IFN-γ is an important diagnostic marker for TB [23, 26]. In the present study, IFN-γ and IL-22 were increased in tubercular pleural fluid.