02–0.03 and p = 0.0079, respectively; Mann–Whitney test). The majority of the CD3+CD8+CD4− T cells co-expressed CD25, LAG-3, CCL4, and/or Foxp3 in combination with CD39, such that CD39 appears to be a preferential marker of CD8+ Treg cells expressing multiple Treg-associated markers (p = 0.0625; Wilcoxon signed-ranks test). To determine the possible suppressive function of CD39+ T cells, CD39-positive and BYL719 cost -negative T-cell

populations were FACS-sorted and tested for their capacity to inhibit the activity of an unrelated CD4+ Th1 responder clone, recognizing a cognate peptide presented in the context of HLA-DR3 [8, 34]. CD8+CD39+ T cells, purified to ≥97% purity, indeed suppressed the proliferative response of (cloned) CD4+ Th1 cells in response to peptide in the context of HLA-class II. This suppressive activity was strongly enriched in the CD8+CD39+ T-cell population as compared with CD8+CD39− T cells and unsorted CD8+ T cells (Fig. 3A). Flow cytometric analysis of sorted T-cell lines demonstrated

enrichment for LAG-3, CD25, Foxp3, and CCL4 in the CD8+CD39+ compared with the CD8+CD39− T cells (Fig. 3B). CD8+CD39+ T cells preserved their expression of CD39 (≥99%), as well as of other Treg-cell markers, including CD25, Foxp3, and CCL4 (Supporting Information Fig. 2) following further in vitro expansion. We next tested the ability of ARL 67156 trisodium GW-572016 salt hydrate (ARL) and the anti-CD39 monoclonal antibody BY40/OREG-103 to reverse the suppressive activity of CD8+CD39+ T cells. ARL is an ATP analog that can bind to, but is not hydrolyzable by, CD39 [35], and has been used to inhibit the suppressive activity of CD4+CD25+CD39+ cells [27]. Here, ARL partially reversed the capacity of CD8+CD39+ T cells to suppress the proliferative Buspirone HCl responses of the Th1 responder clone (14–47% reversal of suppression; in three cell lines; p = 0.023; Wilcoxon signed-ranks test) (Fig. 4). Suppression

by the CD8+CD39+ T cells was also (partially) reversed by the anti-CD39 blocking monoclonal antibody BY40/OREG-103 [36, 37] (0–35% reversal of suppression; in four experiments; p = 0.005; Wilcoxon signed-ranks test) (Fig. 5); further supporting the direct functional involvement of CD39 in suppression mediated by CD8+CD39+ Treg cells. To exclude that suppressive activity by CD8+CD39+ T-cell lines was due to lysis rather than active suppression of the CD4+ Th1 responder clone, the Th1 responder clone and an equal number of cells of an irrelevant T-cell clone were labeled with low and high doses CFSE, respectively, and were added in equal numbers to the coculture assay, identical to previously described [13].

38 Both studies support the hypothesis that improvements in solute clearance

and extracellular fluid volume control during sleep can improve or possibly cure SA. Additionally, case reports have described renal transplantation as a cure for SA presumably due to the elimination of the uremic milieu.39,40 Given the high prevalence of SA in the ESRD population, the clinician Napabucasin datasheet should maintain a low threshold for obtaining a polysomnography with sleep study in patients who complain of poor sleep quality or daytime somnolence. The higher rate of central SA warrants early testing for sleep disturbances. Positive airway devices may be more efficacious than lifestyle modifications such as weight loss because dialysis patients may not have the classic obstructive apnoea features. Continuous positive airway pressure treatment in ESRD has been shown to improve nocturnal oxygenation and daytime alertness in a small study population.41 Once the diagnosis of SA is made, the physician should identify modifiable risk factors. A careful medication history should be performed and attempts should be made to discontinue any

medications that could increase SA risk or worsen the disease. Nocturnal dialysis in the form of HD or night-time PD may be an option if available to improve night-time volume and clearance. Finally, renal transplantation is a goal for many dialysis patients and may represent a possible cure for SA in a subset of patients. Although SA in ESRD is Dynein well described, few studies have evaluated SA prevalence in early CKD or patients not yet on Selinexor dialysis. Markou et al.22 performed sleep studies on 35 patients with creatinine clearance less than 40 mL/min but not on dialysis. SA was present in 54.3% of these patients suggesting that it is also highly prevalent in CKD patients far removed from renal replacement therapy. Another small study by Kimmel et al.12 found SA in all six of the CKD patients that underwent polysomnography. Sleep apnoea prevalence in early CKD was evaluated in one study from large integrated health system.66 Using International Statistical Classification of Diseases and Related Health Problems-9 coding and device

coding for positive airway pressure devices, the study found a 20–40% greater risk of SA in patients with estimated glomerular filtration rate in the range 15–89 mL/min per 1.73 m2 (CKD stages 2–4). These differences were sustained after controlling for possible confounders including diabetes, heart failure and hypertension. While the risk of SA was not increased in patients with lower levels of renal function in this study, those patients had disproportionately higher rates of death and progression to dialysis during the evaluation period and thus were not included in the study cohort. The CKD is a progressive disease that results in higher mortality with advancing stages42 and concurrent SA may lead to greater mortality when the two diseases coexist.

Ex vivo (IFN-γ-producing) and cultured antiviral CD4+ T cells, serum cytokines, and viral loads were measured repeatedly in a cohort of chronically HCV-infected subjects (n = 33) receiving IFN-α. Rapid control of virus indicated by an increased calculated rate of virus clearance, occurred in those subjects demonstrating absent/minimal T-cell responses (p < 0.0006). Surprisingly, in subjects who demonstrated the most robust T-cell responses

(and reduced serum IL-10), there was actually a reduced rate of early virus clearance. A subsequent analysis of NK-cell function in available subjects (n = 8) revealed an inverse correlation between pretreatment NK-cell expression of NKp46 and the potential to upregulate cytotoxic function on exposure to IFN-α (p < 0.004), as well as PI3K inhibitor the subsequent measured rate of viral clearance (p = 0.045). Thus,

the CD4+ T-cell response during IFN-α treatment appears to be shaped by the rate of innate virus suppression. These data suggest that individuals I-BET-762 mouse who respond most effectively to immune intervention may be most in need of subsequent vaccination to prevent reinfection. “
“Tuberculosis is a disease caused by the Mycobacterium tuberculosis complex (MTb). In 2011, global mortality due to tuberculosis was 1·4 million individuals. The only available vaccine is the attenuated M. bovis [bacillus Calmette–Guérin (BCG)] strain, which confers variable protection against pulmonary tuberculosis. Some widely distributed non-tuberculous mycobacteria (NTM), such as M. avium and M. arupense, are also potential pathogens for humans. This work aimed to produce and characterize monoclonal antibodies against the M. bovis BCG Mexico strain of the MTb, M. avium subs. hominissuis and the M. arupense strain from NTM. Hybridomas were produced from splenocytes of BALB/c female mice immunized with radiation-inactivated mycobacteria, and the immunoglobulin (Ig)G2a antibody-producing clones with the

highest antigenic recognition were selected. The selected clones, Mbv 2A10 for M. bovis BCG Mexico, Mav 3H1 for M. avium and unless Mar 2D10 for M. arupense, were used in further studies. Enzyme-linked immunosorbent assay (ELISA) and immune proteomics analyses characterized the clones as having the highest cross-reactivity with mycobacteria. Using mass spectrometry, a number of proteins recognized by the monoclonal antibody (mAb) clones were identified. These proteins had roles in metabolic processes, hypoxia, cell cycle and dormancy. In addition, a Clustal W and Immune Epitope Database (IEDB) in-silico analysis was performed in protein sequences that result in the conserved regions within probability epitopes that could be recognized for Mbv2A10 and Mav3H1 clones. “
“Endosymbiosis is a mutualistic, parasitic or commensal symbiosis in which one symbiont is living within the body of another organism.

The results of inflammatory scoring showed that the increased peribronchial, perivascular, and total lung inflammation after OVA inhalation

was significantly decreased by administration of 2ME2 or CBO-P11 (Fig. 5H). Percentage of airway epithelium, which stained positively with periodic acid-Schiff (PAS) in OVA-treated mice (Fig. 5J, K, and N), was substantially check details greater than in the control mice (Fig. 5I and N). The increased levels of PAS-positive airway epithelium after OVA inhalation were decreased significantly by treatment of 2ME2 (Fig. 5L and N) or CBO-P11 (Fig. 5M and N). To ascertain the inhibitory effect of IC87114 on PI3K-δ, we determined levels of Akt phosphorylation by Western blotting and PI3K activity by phosphatidyl inositol-3,4,5-triphosphate (PIP3) competition enzyme immunoassay. Levels of phosphorylated Akt (p-Akt) protein in lung tissues were significantly increased 48 h after OVA inhalation, as compared with the levels in the control mice (Fig. 6A and B). However, no significant changes in Akt protein levels were observed in any of the group tested. The increased p-Akt, but not Akt

protein, levels in lung tissues after OVA inhalation were significantly reduced by administration C646 of IC87114. Supporting

the results, the increased PIP3 levels in lung tissues after OVA inhalation were significantly decreased by administration of IC87114 (Fig. Levetiracetam 6C). HIF-1α plays an important role in immune and inflammatory responses 8, 9. In fact, HIF-1α is activated oxygen dependently or independently by various mediators including hypoxia, nitric oxide, reactive oxygen species, cytokines, apoptotic cell debris, and infectious pathogens in inflammatory tissues 19–27. Studies have shown that HIF-1α activation during inflammation enhances its target gene expression such as VEGF, glucose transporter 1, and metalloproteinase 20, 28. In addition, a close interaction between HIF-induced glycolytic energy production and immune cell function has been reported 29. HIF-1α activation promotes motility, invasiveness, and bacterial killing of neutrophils and macrophages in bacterial induced inflammation 29. Furthermore, knockdown of HIF-1α gene in dendritic cells reduces glucose utilization and impairs the capability to stimulate T cells 30. One of the target genes of HIF-1α is VEGF, which is known as an important mediator of airway inflammatory diseases 31. However, the roles of HIF-1α and its activation mechanism in allergic airway diseases remain unknown.

S. ratti single infected mice responded to both, S. ratti antigen and polyclonal stimulation by CD3 engagement with IL-10 and IL-13 production whereas L. major single infected mice did not produce these Th2 cytokines (Figure 2b). The IL-10 and IL-13 production in anti-CD3 activated lymphocytes was significantly reduced in co-infected mice compared to S. ratti singly infected mice, although the

mice had been co-infected with L. major for only 2 days. S. ratti antigen-specific proliferation GSI-IX purchase was not affected by co-infection with L. major (Figure 2b). S. ratti antigen-specific IL-10 and IL-13 were reduced by trend but not significantly. Significant IFN-γ production upon anti-CD3 stimulation was observed in L. major single infected but neither in S. ratti single nor in co-infected mice although the CD3-induced proliferation was comparable in all groups. This finding suggests that the transient suppression of IFN-γ response to CD3 engagement, a typical feature of S. ratti-infected mice that we described before (10), was still present in co-infected mice at day 8 post-S. ratti infection. To analyse S. ratti and L. major-specific immune response at the same time, we chose day 16 post-S. ratti infection (i.e. day 10 post-L. major infection) and prepared the mesLN draining the site of S. ratti and the popLN draining the site of L. major infection. No antigen-specific cytokine production

was observed in the mesLN at day 16 p.i., which is in line with the declining immune response at this late stage of infection. Nevertheless, increased IL-10 and IL-13 response BAY 80-6946 mouse to anti-CD3 stimulation were still visible in S. ratti single infected

mice and significantly suppressed in co-infected mice (Figure 2c). Also the S. ratti antigen-specific proliferation was still present in S. ratti single infected mice. L. major infection induced a slight but not significant suppression of this weaker S. ratti antigen-specific proliferation. The suppression PRKACG of IFN-γ response to CD3 engagement that we observed by trend at day 8 post-S. ratti infection in co-infected mice (Figure 2b) was not present at day 16 post-S. ratti infection (Figure 2c), highlighting the transient nature of this suppression (10). Leishmania major-specific and CD3-induced proliferation and IFN-γ production, on the other hand, were not suppressed but even increased in the popLN of nematode co-infected mice while total cell numbers prepared form the popLN ex vivo were comparable (Figure 2d and data not shown). As the proliferation and IFN-γ production by unstimulated popLN were also increased in co-infected mice, the injection of S. ratti iL3 and L. major promastigotes into the same footpad apparently induced a generalized pro-inflammatory milieu. This elevated proliferation and IFN-γ production were still detectable at day 31 post-L. major infection when the footpad swelling started to decrease, indicating successful resolution of infection (Figure 2e).

Identification of T. mentagrophytes CDO provides indispensable tools for future studies of dermatophyte pathogenicity and development of new approaches for prevention and therapy. “
“This article reports a new case of protothecosis by Prototheca wickerhamii in goats. The animal presented severe respiratory difficulty and nodules, sometimes ulcerated, in the nasal vestibule, mucocutaneous junction of the nostrils and skin of the face. Prototheca wickerhamii was isolated from the lesions. The animal had no clinical or haematologiccl evidence of immunodepression. The

agent was highly resistant to antimicrobial drugs. The goat was treated unsuccessfully with fluconazole and euthanised 10 months after the diagnosis of the disease. Histological lesions high throughput screening compounds were necrotising Acalabrutinib cost pyogranulomatous dermatitis, rhinitis and osteomyelitis with myriads of walled sporangia characteristic of P. wickerhamii. It is suggested that in goats, protothecosis is characterised by a chronic, slowly progressive infection, which affects immunologically competent goats, causing multifocal, ulcerative, pyogranulomatous and necrotising lesions of the mucosa of the nasal vestibule, mucocutaneous junctions of the nostrils and skin of the face. “
“Basidiobolus ranarum (Entomophthoromycotina) very rarely

affects the gastrointestinal (GI) tract. To date, reported paediatric GI basidiobolomycosis cases are 27 worldwide; 19 from Saudi Arabia and 8 from other parts of the world. Often these cases present a diagnostic dilemma, are prone to misdiagnosis and lack of disease confirmation by proper molecular methodologies. The fungal mass removed by surgery is usually sent for conciliar histopathology, isolation by fungal cultures and final molecular testing for basidiobolomycosis. The incidence of basidiobolomycoses, their predisposing factors and the molecular diagnosis of the fungus causing the disease in combination

with a phylogenetic framework are reviewed. Basidiobolomycosis is an unusual, rare fungal skin infection causing chronic subcutaneous zygomycosis.[1, 2] It is caused by Basidiobolus ranarum (Entomophthoromycotina)[3, 4] with human disease concentrated Exoribonuclease in tropical and subtropical regions. Extracutaneous involvement is extremely rare[5] with gastrointestinal (GI) involvement being exceedingly rare[6-10]; with only 66 adult and 27 paediatric cases reported worldwide. Most adult cases, 19 patients, were from the United States of whom 17 [89%] were from Arizona[11]; whereas 14 patients were from Iran,[11] 12 patients from Iraq,[12] 11 from the Kingdom of Saudi Arabia (KSA)[11] and 4 from Brazil.[11] The remaining six patients were one from each of Nigeria, India, Bangladesh, Italy, Netherlands and one with unreported country of origin.[11] The 27 reported paediatric patients are summarised in Table 1,[12-24] where 19 patients are from KSA, 3 from Iran, 2 from Iraq, 2 from Brazil and 1 from Nigeria.

Moreover, we demonstrate that steady levels of cska-TCRs are expressed on the cell surface throughout a long-term activation GDC-0980 mouse process, even though they are subjected to lysosomal degradation. This phenomenon is most likely due to the large pool of this receptor

form accumulated within cells during activation. This is in contrast to the non-cska-TCRs that are degraded upon activation and are practically absent from the T-cell surface. These results suggest that sustained TCR-mediated signaling [11] observed even after the majority of receptors have been degraded is due to the cska-TCR population. Our data and the cumulative knowledge on IS formation and maintenance at the T-cell–APC

contact interface lead us to assess the effect of the mutated ζ on immediate and long-term activation processes. We found that although the MUT cells are capable of initiating immediate TCR-mediated signaling events as reflected by the induction of cska ζ isoforms, ZAP-70 and LAT phosphorylation, they synthesized and secreted significantly less IL-2 when compared to the WT cells. These results suggest that the proximal TCR signaling pathway is uncoupled from distal events following modulation of the actin cytoskeleton binding due to the ζ mutations. Following TCR-mediated activation, the MUT cells as well as their corresponding APCs, expressed much lower levels of the CD25 Thiamine-diphosphate kinase and CD69 activation markers, when compared with the WT cells LY294002 mouse and their activating APCs. CD25 and CD69 are expressed

on T cells and other leukocytes 3 to 16 h following activation [25]. Thus, lack of IS formation in the MUT cells disables “cross talk” between the cells, and results in a weak stimulation and aberrant long-term activation of both T cells and APCs. Interestingly, recent studies reported that ζ possesses various positively charged phosphoinositide-binding residues of which in part overlap with the RRR motifs described herein [26-28]. In these studies, mutations in such residues impaired TCR clustering, similarly to our results when mutating the two RRR motifs. Thus, binding phosphoinosidies and actin within the cell could be mediated in parallel by positively charged motifs positioned at various regions of ζ and affect IS formation. However, of particular significance are the two RRR motifs we have identified since we found that they mediate the association between the TCR and the cytoskeleton in resting and activated T cells and are required for IS maintanace for the execution of long activation events, while the mutations described by Zhang et al. [28] showed dissociation of ζ from the membrane upon activation and the role in IS formation and maintenance was not discussed.

47 Thus, JSRV Env is a dominant oncoprotein; however the mechanisms of cell transformation induced by the JSRV Env are not completely understood. Although the mitogen-activated protein kinase (Ras-MEK-MAPK), Rac1, and phosphoinositide 3-kinase (PI3K-AKT-mTOR) pathways are implicated in JSRV-induced cell transformation, it still remains to be determined how the cytoplasmic tail engages the cell signaling network to

activate these pathways.50–54 The majority of the 27 enJSRV proviruses are Sotrastaurin defective as a result of deletions, nonsense mutations, and recombinations; however, five enJSRV proviruses contain intact genomes with uninterrupted open reading frames for all the retroviral genes (Fig. 1).6 These enJSRV loci are insertionally polymorphic in the domestic sheep population. JSRV and enJSRVs have an overall high degree of similarity (approximately 85–89% identity

at the nucleotide level). The evolutionary history of these proviruses together with ruminants suggests selleck that integration of enJSRVs began before the split between the genus Ovis and the genus Capra, approximately 5–7 million years ago, and continued after sheep domestication (approximately 10,000 years ago).6,7 Interestingly, one enJSRV provirus, enJSRV-26, is thought to have integrated in the host <200 years ago and may be a unique integration event occurred in a single animal.6 Thus, the enJSRVs are most likely still invading the sheep genome. In sheep, the morula-stage embryo enters the uterus by day 5 after mating and forms a blastocyst by day 6 that contains a blastocoele surrounded by a monolayer of trophectoderm.55,56 By day 9, the blastocyst hatches from the zona pellucida, develops into an ovoid conceptus by day 12, and then begins to elongate (reaching 25 cm or more by day 17). Elongation of the conceptus is critical for the production of interferon tau (IFNT), which is the pregnancy recognition signal

needed to maintain progesterone production by the corpus luteum, and also for the onset of implantation.57 Niclosamide Implantation of the conceptus involves the apposition, attachment, and adhesion of the conceptus trophectoderm to the endometrial luminal epithelium (LE) of the uterus. Within the outer layer of the conceptus termed the chorion, binucleated trophectoderm cells, termed trophoblast giant binucleate cells (BNC), begin to appear as early as day 14.58 The BNC are thought to be derived from the mononuclear trophectoderm cells by a process referred to as mitotic polyploidy, which involves consecutive nuclear divisions without cytokinesis.59 BNC then fuse with uterine LE to form trinucleate fetomaternal hybrid cells.58 Other BNCs fuse with the trinucleate cells (and likely each other) to form plaques of multinucleated syncytiotrophoblast that have 20–25 nuclei. Trophoblast BNC of the sheep placenta are analogous in many ways to the giant cells of the syncytiotrophoblast of the human placenta.

ASTRAL enrolled 806 patients from 56 centres with a mean follow up of 34 months (total follow up was 5 years reported for a small number of patients).3 The average degree of RAS was 76% and the 5-year

mortality in the whole group was 51%. Methodological issues that have been raised include: 1 ASTRAL recruited patients in whom there was ‘uncertainty about the value of revascularization  . . .’. This was considered a strength by the authors, because it represented the ‘real world’ situation. However, it may lead to an ascertainment bias in favour of medical therapy because patients with the highest grade of stenosis may not have been entered into the study but treated with revascularization. www.selleckchem.com/products/PLX-4032.html Finally, the lack of robust evidence for or against angioplasty use is further negated by the 9% perioperative complication rate and the 20% 1 month complication

rate in the intervention arm in ASTRAL. The DRASTIC study,5 the largest published RCT, enrolled 106 patients with hypertension, high-grade atherosclerotic RAS and a serum creatinine concentration Estrogen antagonist <200 µmol/L. Patients were randomly assigned to undergo percutaneous transluminal renal angioplasty (PTRA) or to receive antihypertensive drug therapy, followed by balloon angioplasty (if needed) at 3 months. Overall BP and renal function were similar in the two groups at 3 and 12 months, although angioplasty reduced the need for one additional daily antihypertensive agent. However, after subgroup analysis, it was found that in patients with bilateral stenoses, the creatinine clearance improved in the angioplasty group, but fell in patients assigned to the delayed intervention group. This was at a cost of 11% peri-procedural morbidity. A Scottish group reported a prospective randomized trial of percutaneous angioplasty versus medical therapy in patients with bilateral or unilateral atherosclerotic RAS and sustained hypertension.6 In the bilateral group (n = 28), the drop in systolic pressure was significantly larger following

angioplasty than following medical therapy, but diastolic pressure and creatinine Thymidylate synthase after 24 months were not different with either intervention. In the unilateral group (n = 27), there was no difference in serum creatinine or BP control between angioplasty and medical therapy. This was at a cost of 25% peri-procedural morbidity. In the EMMA study reported by Plouin et al.,7 hypertensive patients were randomly assigned antihypertensive drug treatment (n = 26) or angioplasty (n = 23). They also found that BP at 6 months did not differ between control (141 ± 15/84 ± 11 mmHg) and angioplasty (140 ± 15/81 ± 9 mmHg) groups. Angioplasty reduced the requirement for antihypertensive therapy at the cost of some procedural morbidity of 25%. van der Ven et al.

DCs are heterogeneous and include both several

conventional DC subsets and plasmacytoid BAY 57-1293 mouse DCs. Conventional DCs, highly specialized APCs that can activate naïve T cells, are characterized by their strong expression of MHC II and CD11c. In addition to these DCs that are present during the steady state, infection or inflammation induces some other DC subsets [4, 5]. Infection with L. monocytogenes induces recruitment of a monocyte-derived DC subset (TipDC) that can produce TNF-α and iNOS in the spleen and mediates innate immune defense against the pathogen [6]. DCs with regulatory functions have also been described. CD11clowCD45RBhigh DCs produce large amounts of IL-10 and are capable of suppressing T cell responses and inducing differentiation of Type 1 regulatory T cells [7]. Modulation of the function of DCs during Plasmodium infection has been the subject of several investigations [8]. RBCs that are infected with P. falciparum adhere to DCs and inhibit their maturation, reducing activation of specific T cell immune responses [9]. With progress of

the blood stage of infection, maturation of DCs and their ability to activate adaptive immune responses are inhibited and their ability to secrete IL-12/IL-10 in response to Toll-like receptor signaling is reversed [10-12]. Studies of DC subsets have indicated that during P. yoelii infection regulatory DCs become the most prevalent DC population. These cells preferentially induce IL-10-producing CD4+ T cells and inhibit excessive immune responses BMS-777607 price during systemic infectious diseases [13]. In a model of P. chabaudi infection, researchers demonstrated that CD8+ DCs are the major DC population during the early phase of infection, whereas CD8− DCs play a major role in the later phase of infection and promote IL-4- or IL-10-producing CD4+ T cells [14]. The spleen is the major organ involved in generating protective immune responses during malarial infection [15]. Splenectomy of ZD1839 research buy mice immune to P. vinckei vinckei showed the critical role played by the spleen [16]. The mice lost their protective

immunity after splenectomy because of depletion of CD4+ T cells. Splenomegaly is a prominent symptom of malaria. The size of the spleen dramatically increases during Plasmodium infection because of influx and expansion of immune cells together with hematopoiesis. The microarchitecture of the spleen is also altered during malarial infection [17, 18]. However, the mechanisms by which protective immunity is generated in the spleen during infection are not clearly understood. Given the significant changes in splenic cellular composition and activation of immune cells by systemic inflammation that accompany Plasmodium infection, we postulated that the non-DC population may function as APCs during infection with Plasmodium species. Because expression of MHC II is obligatory for activating CD4+ T cells, we investigated MHC II+CD11c− non-T, non-B cells, which accumulate in the spleen during P.