1), in which S1PR5 plays a role in BM egress [16]. To investigate the function of S1PR5 in monocytes, we first compared the percentage of

monocyte subsets in the blood of wild-type (WT) and S1pr5−/− mice [18] by flow cytometry. Results in Figure 2A–C showed a significant reduction of Ly6C− monocytes in the blood of S1pr5−/− mice. This reduction was observed both in S1pr5−/− female (Fig. 2A and B) and male mice (Fig. 2C). S1pr5+/− heterozygous mice also showed a mild phenotype (Fig. 2B). A strong reduction in the frequency Selleckchem H 89 of Ly6C− monocytes was also observed in the spleen, which is known to be an important reservoir for this subset [19] (Fig. 2D), in the lymph nodes and in non-lymphoid organs such as the lung, liver, and kidney (Fig. 2E). By contrast, the percentage of Ly6C− monocytes appeared normal in the BM of S1pr5−/− mice (Fig. 2F). Moreover, the percentage of Ly6C+ monocytes was normal in

all lymphoid organs of S1pr5−/− mice tested (Fig. 2, all panels). To test if the role of S1PR5 in monocytes was cell-intrinsic, we generated mixed BM chimeras by reconstituting lethally irradiated mice with equal amounts of BM from WT (CD45.1+) and S1pr5−/− (CD45.2+) mice. Six weeks after reconstitution, we measured CD45.1 and CD45.2 expression in different immune subsets in the blood and BM, and calculated the corresponding S1pr5−/− to WT ratio for each subset. As previously reported [20], for www.selleckchem.com/products/azd2014.html mature NK (mNK) cells, this ratio was very high in the BM and very low in the blood (Fig. 3, left panel), reflecting the important role of S1PR5 in NK cell exit from the BM. For Ly6C+ monocytes, the S1pr5−/− to WT ratio was

nearly 1 in both blood and BM (Fig. 3, right panel), confirming the absence of a role of S1PR5 in this subset. By contrast, for Ly6C− monocytes, the S1pr5−/− to WT ratio was near 0.5 in the BM and 0.1 in the blood (Fig. 3, left panel). These data suggest that S1PR5 is important both for the development of Ly6C− monocytes and for their trafficking or their survival CYTH4 at the periphery. The paucity of patrolling monocytes in the periphery of S1pr5−/− mice could be explained by a role of this receptor either in their egress from the BM or in their survival at the periphery. To try and discriminate between both hypotheses, we performed a series of experiments using Cx3Cr1gfp/gfp and Ccr2−/− mice as controls. Indeed, CX3CR1 has been shown to regulate peripheral survival of patrolling monocytes but is devoid of chemotactic activity involved in BM egress. Reciprocally, CCR2 is essential for monocyte egress from the BM but is not involved in their survival. The distribution of Ly6C− monocytes in Cx3cr1gfp/gfp and Ccr2−/− mice is in fact very similar to that of S1pr5−/− mice, with a near normal frequency in the BM and a low frequency of these cells at the periphery (Fig. 4A).

All these inflammatory mediators together play a crucial role in the orchestration of an inflammatory response, particularly in neutrophil recruitment, representing a different type of effector OTX015 cell line cells. Neutrophil sequestration and migration into alveoli remain pathohistological hallmarks of ARDS, with neutrophils being key effector cells, which further destruct lung tissue [6]. The process of programmed cell death, or apoptosis, is known to play a major regulatory role in maintaining many biological processes, not least of which is the inflammatory response, such as in ALI/ARDS. Two major apoptosis pathways

in mammalian cells are known so far: (i) the intrinsic or mitochondrial pathway with involvement of Bcl-2 at the outer membrane of mitochondria, cytochrome c release and activation of caspase-9; and (ii) extrinsic or death receptor pathway with activation of caspase-8 upon binding of death activator to Fas- and tumour necrosis factor (TNF)-receptor at the surface of the cell. Both pathways converge at the level of caspase-3 activation [7]. Apoptosis results in destruction of proteins by caspases as well as in fragmentation of the DNA. Finally, apoptotic cells are eliminated by phagocytes.

Inappropriate activation or inhibition of apoptosis can lead to disease either because ‘undesired’ cells develop prolonged survival or because ‘desired’ cells die prematurely [8]. The purpose of this study was to evaluate in vitro apoptosis rate and pathway of effector and target cells at different time-points upon injury with endotoxin and hypoxia, both factors Roflumilast which SB431542 ic50 might contribute to ALI in vivo. We were interested to

assess if upon injury different cell types undergo apoptosis in a similar way. Our hypothesis was that within the group of effector or target cells, the cells would experience the same kind of apoptosis. Specific pathogen-free male Wistar rats (250–300 g) were purchased from Janvier (Le Genest-St Isle, France). Rats were anaesthetized with subcutaneously administered Narketan (ketamine 10%, Kepro, Utrecht, the Netherlands) 0·8–1 ml/kg and Rompun (Xylazin 2%, Streuli Pharma, Uznach, Switzerland) 0·25–0·5 ml/kg. All animal experiments and animal care were approved by the Swiss Veterinary Health Authorities. Alveolar macrophages (CRL-2192; American Type Culture Collection, Rockville, MD, USA) were established from normal Sprague–Dawley rat alveolar macrophage cells obtained by lung lavage, cloned and subcloned three times. The cells exhibit characteristics of macrophages and are sensitive to endotoxin. Cells from passages not higher than 5 were used. Cells were cultured in nutrient mixture F-12 Ham (Ham’s F-12; Invitrogen Corporation, Carlsbad, CA, USA), completed with 15% fetal bovine serum (FBS), 5% penicillin/streptomycin (10 000 U/l) and 5% HEPES. Overnight, before starting the experiments, cells were incubated with Ham’s F-12 with 1% FBS.

6A). In E-Btk-2 and EY-Btk-5 mice IgM serum levels were increased (Fig. 6B), consistent with the presence of increased numbers of IgM ASC in the long-lived compartment in the BM. The E-Btk-2 and EY-Btk-5 mice did not

show an increase in ASC of other subclasses (data not shown), and accordingly serum levels were either decreased or in the WT ranges (Fig. 6B). To investigate mature B-cell functionality, we analyzed the immune response to the T-cell independent type II (TI-II) antigen, TNP-Ficoll and the T-cell dependent (TD) antigen, TNP-KLH. Consistent with previous reports 8, 23 Btk-deficient mice did not show TI-II IgM or IgG3 responses (Fig. 6). Similarly, click here E-Btk-2 mice were unresponsive to TNP-Ficoll immunization, whereas EY-Btk-5 mice responded similarly to WT mice (Fig. 6C). The response to the TD

antigen TNP-KLH was assessed 1 wk after immunization (IgM) and 1 wk after booster immunization (IgG). WT and Btk-deficient mice had similar primary IgM and secondary IgG1 responses (Fig. 6D), but these were severely reduced in E-Btk-2 and EY-Btk-5 mice. Consistent with defective TD responses, clusters of PNA+ germinal center B cells were not detectable (E-Btk-2) or severely reduced (EY-Btk-5) in immunohistochemical analyses (data not shown). In summary, these findings demonstrate that both E-Btk2 and EY-Btk5 Tg efficiently drive IgM+ plasma cell differentiation, but this is not associated with increased functional TI-II responses. Moreover, TD responses and germinal center

formation were Y-27632 2HCl significantly affected by the presence of constitutive active Btk. As the E-Btk-2 and EY-Btk-5 B cells were spontaneously driven into germinal center-independent Selumetinib purchase plasma cell differentiation, the Btk Tg mice may have lost self-tolerance. In serum of 9–12 wk old animals we found that anti-nucleosome-specific IgM was increased in E-Btk-2, but not in EY-Btk-5 mice, to levels that were similar to those found in autoimmune MRL/lpr control mice (Fig. 7A). No anti-nucleosome IgG was detectable in WT or Btk Tg mice. Serum analysis of ∼35 wk old mice revealed that total IgM levels increased with age and that IgM serum levels in E-Btk-2 and EY-Btk-5 mice remained dramatically elevated compared with values in WT mice (Fig. 7B). Strikingly, E-Btk-2 mice had developed dramatically increased anti-nucleosome IgM, which was at least >15 times the level found in MRL/lpr mice (Fig. 7C). Also in YE-Btk-5 mice anti-nucleosome activity was detectable, but concentrations were lower. Overexpression of unmutated human Btk (in Btk-2 mice, also under the control of the CD19 promoter 28) or high-level expression of E41K-Btk (in E-Btk-3 mice) did not induce anti-nucleosome IgM (Fig. 7C). Although immunohistochemical stainings of kidneys revealed the presence of enlarged glomeruli containing IgM deposition in E-Btk-2 Tg mice (Fig. 7D), we did not find evidence for autoimmune disease, such as proteinuria or glomerular inflammation.

How this extracellular pathogen is able to evade the host immune response for such long periods of time is currently unclear. To gain a better understanding of how this organism persists in the infected human, many laboratories have focused on identifying and characterizing outer surface proteins of B. burgdorferi. As the interface between B. burgdorferi and its human host is its outer surface, proteins localized to the outer membrane must play an important role in dissemination,

virulence, tissue tropism, and immune evasion. Over the last two decades, numerous outer surface proteins from B. burgdorferi have been identified, and more recent studies have begun to elucidate the functional role(s) of many borrelial outer surface proteins. This review summarizes the outer surface proteins identified in B. burgdorferi to date and provides detailed insight into the functions of many check details of these proteins as they relate to the unique parasitic strategy of this spirochetal pathogen. Lyme disease, or Lyme borreliosis,

is an arthropod-borne infection caused by the pathogenic spirochete Borrelia burgdorferi (Benach et al., 1983; Steere Dorsomorphin et al., 1983). Since its discovery in 1975, during an epidemic of oligoarthritis in children and adults (Steere et al., 1977b), Lyme disease has become recognized as the most prevalent arthropod-borne infection in the United States (Centers for Disease Control, 1996). Lyme disease is typically transmitted to humans by the bite of an infected Ixodes spp. Tick, and the earliest

manifestations include a skin rash, termed erythema migrans, with concomitant flu-like symptoms (Steere et al., 1977a). Infected individuals that do not receive antibiotic therapy are at risk for developing chronic forms of the disease which can result in various disorders of the heart, nervous system, and joints. Although this disease is endemic to the East Coast, Upper Midwest, and Pacific coast of the United States, Lyme disease is also widespread throughout many parts of Europe (Barbour & Fish, 1993; Lovrich et al., 1994). The recent increase in the number of Lyme disease cases being reported from various Cobimetinib mouse areas of the United States and Europe, (Barbour et al., 1996; Moody et al., 1998), underscores the importance of generating a new and efficacious Lyme disease vaccine. In this regard, the outer surface lipoprotein A (OspA)-based vaccine for Lyme disease, which was approved for human vaccination for several years, was taken off the market almost a decade ago and is no longer in use. Therefore, the identification of new outer surface proteins that could be used as a second-generation vaccine is now not only warranted for basic scientific reasons, but also is important for overall public health. Antibodies directed against outer surface proteins (e.g.

Mast cells play a key role in allergic and inflammatory reactions. Mast cells and some tumour cell lines such as RBL-2H3 express the high-affinity IgE receptor (FcεRI) on their cell surface. FcεRI is a member of the multichain immune recognition receptors (MIRRs), including T- and B-cell receptor. With regard to OVA-challenged and IgE-mediated mast cell degranulation, FcεRI aggregation activates phospholipase Cγ to increase IP3 generation. The IP3 Silmitasertib ic50 causes Ca2+ release from the endoplasmic reticulum through IP3 receptors, which consequently

results in a large amount of Ca2+ influx via SOCs, leading to mast cell degranulation. In the present study, we demonstrated for the first time that parallel to enhancement of food allergen–induced mast cell degranulation, OVA-mediated Ca2+ entry through SOCs was increased. Given that increasing Ca2+ entry through SOCs enhances mast cell degranulation [20], we conclude that increase in Ca2+ entry through SOCs contributes to food allergen–mediated mast cell degranulation. The two membrane proteins, STIM1 and Orail, have been shown to be essential for the activation of SOCs [16]. Overexpression of Orai1 together with STIM1 has been suggested to upregulate Ca2+ entry through SOCs upon stimulation. In this study, we found that both mRNA and protein expressions levels of Orai1 and

STIM1 in mast cells were increased in OVA-sensitized animals, which is proposed to be an important reason accounting for the increase in SOC-mediated Ca2+ entry and mast cell activation. It has been suggested that the N-terminal A 769662 of STIM1 is glycosylated and translocated from endoplasmic reticulum to the cell membrane when the calcium store is depleted, which process is

required for activation of SOCs [30]. This is in line with our study as the translocation of STIM1 protein to activated mast cell membrane in OVA-sensitized mast cells. Therefore, our study demonstrates for the first time that overexpression and activation of SOCs contributes to enhancement of Ca2+ entry through SOCs in food-allergic rats. Activated mast cell can release a diverse array of biologically active products, including preformed granule contents, the de novo synthesis of eicosanoids, Bupivacaine cytokines, chemokines and free radicals (such as ROS) [31]. Large amount of ROS has been demonstrated to generate in inflammatory cells during asthma, but little information is known in the situation of food allergy. A number of studies report that ROS are involved in the signals leading to degranulation and cytokine secretion in mast cells [32, 33]. In this study, we found that ROS production was significantly increased in the peritoneal lavage solution. Using Ebselen to partially scavenge ROS production (mainly hydrogen peroxide), Ca2+ entry through SOCs was inhibited.

8 ± 0.2 seconds (1As: 3.0 ± 0.3 seconds and 3As: 2.6 ± 0.3 seconds) and time-to-peak (TP) of 8.2 ± 0.7 seconds (1As: 10.3 ± 1 seconds and 3As:5.7 ± 0.5 seconds). No significant differences were detected for all parameters between 1As and 3As for NSC 683864 cell line KCl or Ado application, while 1As had a significantly longer TP and greater peak dilation than 3As to Ach. These findings demonstrate that 1As and 3As from the rat G muscle

appear to have similar responsiveness to vasoactive agonists. Furthermore, the average TD before vasodilation supports a role for metabolic signals as contributors to the ROV. “
“The dephosphorylation of myosin by the MP causes smooth muscle relaxation. MP is also a key target of signals that regulate vascular tone and thus blood flow and pressure. Here, we review studies from the past two decades that support the hypothesis that the regulated expression of MP subunits is a critical determinant of smooth muscle responses to constrictor and dilator signals. In particular, the highly regulated splicing of the regulatory subunit Mypt1 Exon Ruxolitinib in vivo 24 is proposed to tune sensitivity to NO/cGMP-mediated relaxation. The regulated transcription of the MP inhibitory subunit

CPI-17 is proposed to determine sensitivity to agonist-mediated constriction. The expression of these subunits is specific in the microcirculation and varies in developmental and disease contexts. To date, the relationship between MP subunit expression and vascular function in these different contexts is correlative; confirmation of the hypothesis will require the generation of genetically engineered

mice to test Rho the role of MP subunits and their isoforms in the specificity of vascular smooth muscle responses to constrictor and dilator signals. “
“Please cite this paper as: Fry BC, Lee J, Smith NP, Secomb TW. Estimation of blood flow rates in large microvascular networks. Microcirculation 19: 530–538, 2012. Objective:  Recent methods for imaging microvascular structures provide geometrical data on networks containing thousands of segments. Prediction of functional properties, such as solute transport, requires information on blood flow rates also, but experimental measurement of many individual flows is difficult. Here, a method is presented for estimating flow rates in a microvascular network based on incomplete information on the flows in the boundary segments that feed and drain the network. Methods:  With incomplete boundary data, the equations governing blood flow form an underdetermined linear system. An algorithm was developed that uses independent information about the distribution of wall shear stresses and pressures in microvessels to resolve this indeterminacy, by minimizing the deviation of pressures and wall shear stresses from target values.

We hope for continuous EFIS-EJI support for future meetings, which is indispensable as it provides travel grants for a significant number of young immunologists who attend the conference. The next conference is planned for September 2012 and the details will be posted on http://www.img.cas.cz/tatra/ approximately one year in advance of the meeting. Perhaps we will see you there. Radek Špíšek Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic e-mail: [email protected]

“
“The behavior of self-reactive T cells ABT-888 mouse in the peripheral immune system has often been studied by following the fate of adoptively transferred antigen-specific T cells in antigen expressing mice. In most cases, after a period of expansion, such cells undergo a slow clonal deletion, accompanied by the onset of anergy and/or suppression in the remaining cells. Here, we demonstrate that at initial frequencies approaching those found in normal repertoires, it is possible to completely avoid deletion Z-IETD-FMK price and still maintain peripheral tolerance. At starting numbers of <1000 T cells, stimulation by chronic self-antigens resulted in a period of robust clonal expansion, followed by a steady plateau phase extending

beyond 4 months. Despite their Tenoxicam stable persistence, the self-reactive T cells did not convert to a Foxp3+ fate. However, they displayed a considerable block in their ability to make IL-2, consistent with the onset of anergy — in a precursor frequency or deletion independent fashion. In an adaptive immune repertoire, the frequency of T cells that are specific for any given pathogen is thought to be very low. Although the precise numbers are difficult to estimate, in the mouse, it is thought to range in frequency from 1/1000 to 1/100,000 [1, 2] and numerically as low as 20 per mouse [3, 4]. The robust clonal expansion and differentiation that follows antigen recognition in vivo, is therefore geared to expanding

these rare precursors to large numbers of potent effector cells, in a short amount of time. However, the same process can be lethal if the target epitope is derived from a self-antigen. Therefore, the vertebrate has evolved several processes to curtail self-reactive T cells. After central tolerance deletes a large proportion of these, very few escape to the periphery. This makes it even more difficult to isolate and follow their behavior in unmanipulated animals (until an autoimmune process activates and expands them). Instead, we and others have routinely used adoptive transfer model systems that infuse a traceable population of self-reactive T cells into mice and follow their fate.

This lack of knowledge has necessitated the use of immunosuppressive agents for the treatment of chronic immunological disorders. Additional treatment options aiming to suppress or eliminate immunological cell lines are presently in vogue [28–35]; however, these continue to be unable to provide Selumetinib research buy specific treatment, and are not without untoward injurious effects. It is believed that through appropriate presentation of endogenous ag [30], autoimmune diseases and cancer could be treated specifically, without

the use of drugs. Various attempts have been made to achieve this goal and accomplish such a treatment modality. The introduction of soluble tissue ag through various routes, especially for the prevention of certain experimental autoimmune diseases, has proved to be beneficial [36–41]. However, when a similar technique was employed to treat animals or patients with established autoimmune diseases, beneficial

outcomes were not observed [42, 43]. Normal tissue constituents, injected into animals in an aqueous form, will not evoke an autoimmune disease, but will result in a non-pathogenic immune response manifesting in specific IgM aab production against the injected ag [9, 44]. However, if the same ag is injected in a chemically modified form [9], it will initiate and (if the chemically modified ag is repeatedly administered) maintain a pathogenic IgG aab response. We firmly believe that most autoimmune diseases originate not by the spontaneous emergence of autoreactive

T cells, but by abnormal KPT-330 chemical structure presentation of self [9, 12, 21, 45]. Agents that can change the chemical composition of autoantigens (aag) from self to altered self include drugs, chemicals, toxins, denaturing agents, etc. T cells that continuously circulate in the blood are also present in the extravascular space survey for normalcy. If an endogenous or exogenous-like (i.e. modified self ag) or a molecule similar to a self ag (molecular mimicry) is detected in the circulation or at a certain location, then the cells of the immune system DNA ligase will respond to the altered self ag with a pathogenic IgG aab response. If the altered self ag persists in the system, then a chronic progressive disorder will ensue resulting in a definable autoimmune disease. Cancer-specific ag on cancer cells are minimally antigenic and low-MW molecules. Their presentation as part of apoptotic cellular breakdown products – following cancer cell death because of ischaemia – will only evoke a non-pathogenic IgM aab response [17] (which facilitates the removal of cancer cell breakdown products from the system by phagocytic cells) but no pathogenic aabs against the cancer-specific ag. Presentation of an ag, whether exogenous or endogenous, will determine the immune response outcome. Aag per se will not initiate pathogenic disease causing aab production [9]. However, if a self ag becomes chemically modified (e.g. by toxins, drugs, smoking, alcohol, trauma, UV irradiation. etc.

Comparisons with other Omp85s showed that the membrane domain is most conserved, whereas the periplasmic domain is more variable [23]. Interestingly, the protective activity of the Omp85 homolog, D15, from H. influenzae seemed to reside in the periplasmic part [21], suggesting that this part may be more important as a vaccine antigen. Possibly, the essential role of Omp85 in protein transport shields the membrane domain from interactions with the immune system. We used deoxycholate-extracted Tyrosine Kinase Inhibitor Library cell line OMVs for this study as

such vaccines are safe and efficacious in protection trials [2-4]. Most of the lipopolysaccharides (LPS), phospholipids and lipoproteins are removed by the detergent, which may possibly alter the conformation of Omp85 and other outer membrane antigens [53], as well as exposing epitopes that are masked in the Deforolimus in vivo native membrane. However, studies with native OMVs, in which outer membrane proteins are likely to be in their native conformation, support the notion that Omp85 is most probably non-bactericidal. Mice receiving such vaccines showed

negligible serum bactericidal activity against heterologous serogroup A strains [54], which also express Omp85 [5, 6, 17], as well as against some heterologous serogroup B strains [55]. It might be argued that the overexpressed Omp85 in the Omp85+ OMV vaccine in our study was not properly folded in the outer membrane and so explain why the increased Omp85 antibody levels did not result in higher bactericidal activities compared with the wt control vaccine. However, NMRI mice, immunized with the wt vaccine, showed equally high Omp85 antibody levels and serum bactericidal titres as the other mice strains given the Omp85+ vaccine (Figs. 2A and 3). As bactericidal antibodies are only induced by PorA in a native conformation [56, 57], the distinct bactericidal activity implied that the wt OMV vaccine expressed correctly folded PorA and presumably also

of Omp85. The negligible bactericidal activity of the NMRI sera with the PorA minus mutant showed that Omp85 antibodies did not contribute to the bactericidal activity. SBA with heterologous strains in other OMV vaccine studies also indicated that Omp85 antibodies were Methisazone non-bactericidal [6, 7]. Neither did studies of Omp85 homologs from other bacteria demonstrate bactericidal activity of the specific antibodies although they were protective in animal models [18, 20]. To our knowledge, the only previous study of the vaccine potential of meningococcal Omp85 also found no bactericidal activity in OFI mice vaccinated with detergent-extracted OMVs containing Omp85 overexpressed by another genetic system [16]. Bactericidal activity was only demonstrated when the Omp85 sera were combined with sera following immunization with OMVs containing overexpressed levels of other minor OMPs.

Curr. Protoc. Immunol. 95:14.26.1-14.26.26. © 2011 by John Wiley & Sons, Inc. “
“Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Stockholm, Sweden Department of Cell Biology, selleck products Physiology and Immunology, Biomedicine and Biotechnology Institute, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain The appearance of group 1 CD1 proteins (CD1a, CD1b and CD1c) on maturing myeloid DC is a key event that converts myeloid DC to effective lipid APC. Here, we show that Borrelia burgdorferi, the causative agent of Lyme disease, triggers appearance of group 1 CD1 proteins at high density on the surface of human myeloid DC during infection.

Within human skin, CD1b and CD1c expression was low or absent prior to infection, but increased significantly after experimental infections and in erythema migrans lesions from Lyme disease patients. The induction of CD1 was initiated by borrelial lipids acting through TLR-2 within minutes, but required 3 days for maximum effect. The delay in CD1 protein appearance involved a multi-step process whereby TLR-2 stimulated cells release soluble factors, which are sufficient to transfer the CD1-inducing effect in trans to other cells. Analysis of these soluble factors identified IL-1β as

a previously unknown pathway leading to group 1 CD1 protein function. This study establishes that ICG-001 cost upregulation of group 1 CD1 proteins is an early event in B. burgdorferi infection and suggests a stepwise mechanism whereby bacterial cell walls, TLR activation and cytokine release cause DC precursors to express group 1 CD1 proteins. CD1 proteins have structurally diverse antigen grooves that accept self and foreign lipid antigens for display to T cells 1. The antigenic lipids are amphipathic molecules that include lipids, lipopeptides and glycolipids derived from mammalian cells 2 and microbial sources 3. The human CD1 gene cluster consists of

one lipid transfer protein (CD1e), three group 1 antigen-presenting molecules (CD1a, CD1b and CD1c) and one group 2 antigen-presenting molecule (CD1d) 4, 5. For MHC class II, it is well established that the density of peptide-loaded complexes many changes greatly during DC maturation and controls the strength and antigenic focus of the resulting MHC-restricted T-cell response 6. New evidence suggests that myeloid APC contribute to the immunologic distinction between uninfected and infected state by actively regulating density of cell surface CD1 proteins in response to pathogen contact 7. Although CD1d is constitutively expressed on monocytes and DCs, group 1 CD1 proteins are absent on circulating monocytes, but are inducibly expressed on myeloid DCs after activation 8.