Candida albicans is affected by alpha defensins, LL-37, calprotectin, and HBD1.107,109 In addition, C. albicans is inhibited by both SLPI and Elafin.28 Bacterial vaginosis has been described as a co-factor for HIV

acquisition. Cu-Uvin et al.110 have shown BV to be significantly associated with genital tract shedding of HIV. BV is characterized by loss of the normal protective Lactobacilli and overgrowth of Selleck Midostaurin diverse anaerobes.111 The microorganisms involved in BV are many, but include Gardnerella vaginalis, Mobiluncus, Bacteroides, and Mycoplasma. Low levels of SLPI and an increase in lactoferrin in cervicovaginal fluid have been associated with BV,59,112 The increase in lactoferrin could be attributed to higher levels of neutrophil activation and degranulation, but was not sufficient to protect against HIV infection.59 Elafin decreases in CVL from women with BV.61 Trichomonas is an extracellular protozoa

that adheres to and damages vaginal epithelial cells.113T. vaginalis infection predisposes women to HIV infection and increases HIV shedding in the FRT.114,115Trichomonas vaginalis EPZ-6438 concentration lipophosphoglycans induce a dose-dependent upregulation of IL-8 and MIP3α in vaginal, ectocervical, and endocervical epithelial cells.116 TV Infection by T. vaginalis results in significantly higher concentrations of vaginal fluid neutrophil defensins and cervical IL-8 in women with asymptomatic trichomoniasis compared to uninfected counterparts.55 Multiple distinct species of Lactobacilli colonize the lower genital tract of women. In healthy Edoxaban women of reproductive age, major phylotypes of Lactobacillus includes L. crispatus, L. iners, L. gasseri, L. jensenii, L. gallinarum, and L. vaginialis.117 These commensals play a very important role in maintaining a healthy vaginal ecosystem that protects

women against sexually transmitted pathogens. The presence of Lactobacilli creates an acidic environment that is detrimental to pathogens. In addition, they secrete bacteriocins that directly kill pathogens. Loss of Lactobacilli through illness or antibiotics intake increases a woman’s chance of getting infected by a sexually transmitted pathogen.117 However, in one study, lactobacilli were reported to enhance HIV infection.118 We and others have shown that FRT secretions contain antimicrobials that act either alone or in synergy to inhibit a number of sexually transmitted pathogens (J. V. Fahey, R. M. Rossoll, C. R. Wira, unpublished observation).40,82,84,92,119 Recently, we tested FRT secretions against L. crispatus and found no effects.92 This suggests an intricate balance in which constitutive secretions containing endogenous antimicrobials can affect pathogens but not commensals, which maintain a healthy vaginal ecosystem. Given the number of proteins with antimicrobial properties found in the FRT, it is likely there are many others yet to be discovered. Several promising candidates are shown in Table II.

101 It is known that heavy proteinuria develops with pathological changes of mesangial apoptosis and recruitment of neutrophils and monocytes into the mesangium, followed by release of chemoattractant, pro-inflammatory cytokines and subsequent mesangial hyperproliferation and matrix expansion. Blocking this process is associated with significant reductions in urinary protein

excretion. Panichi’s group were able to ameliorate mesangial inflammation with the administration of 1,25-OHD, which reduced inflammatory BYL719 in vivo cell recruitment and cytokine production (measured as urinary IL-6), together with associated decreases in mesangial cell proliferation.104 Similar results were obtained by Makibayashi’s lab using the same model but with the VDR activating 1,25-OHD analogue 22-oxa-calcitriol (OCT).105 In addition to the cellular changes reproduced, this group also demonstrated a reduction in mesangial matrix, FDA approved Drug Library cell assay with diminished expression of mRNA and staining for type I and IV collagen, and α-smooth muscle actin (α-SMA). This effect may be mediated through modulation of transforming growth factor-β (TGF-β) which is known to modulate mesangial cell proliferation106 and in Makibayashi’s study diseased glomeruli showed strong staining for TGF-β1 with upregulated mRNA expression which was greatly reduced MG-132 molecular weight in the treatment

group.105 This effect on TGF-β had been seen in an earlier study by Schwarz et al. who used subtotally nephrectomized rats as a model of glomerular remodelling and sclerosis.107 In 1,25-OHD-treated diseased rats, the group effectively reduced glomerulosclerosis and mean volume of individual glomeruli – a marker of hypercellularity, matrix expansion and proliferation. This was associated with diminished in situ hybridization for cellular TGF-β, and most importantly a significant reduction in albuminuria.107 The clinical translation of this work has recently been published by the VITAL investigators.108 In this well-designed placebo-controlled, double-blind trial,

281 patients with diabetic nephropathy were randomized to placebo, 1 µg/day or 2 µg/day paricalcitol, in addition to standard renin-angiotensin blockade for 6 months. There was a significant reduction in urinary albumin excretion in the paricalcitol groups compared with placebo which demonstrated a dose–response relationship and was most evident between the placebo and 2 µg/day groups (−3% (95% CI: −16 to 13) vs−20% (95% CI: −30 to −8), P = 0.053). This was accompanied by a substantial, early sustained reduction in eGFR (−3 to −5 mL/min/1.73 m2, P = 0.055) and systolic blood pressure (−3 to −9 mmHg, P = 0.033), implying that paricalcitol may improve albuminuria via suppression of the renin-angiotensin system.

Mucosal mast cells respond to both IgE-dependent (antigen) Y-27632 cell line and non-IgE-dependent (bacterial toxins, neurotransmitters, etc.) stimulation and release a wide variety of bioactive mediators into adjacent tissues and exert their function in the allergic inflammation and in modulation of the gut function [9]. Besides an increased vascular permeability, mucosal oedema and contraction of smooth muscles, a diminished barrier integrity

was observed leading to an antigen-induced enhanced epithelial permeability [10]. These activated mast cells produce Th2-type cytokines, such as IL-3, IL-5 and IL-13 leading to the accumulation of eosinophils and other inflammatory cells relevant to allergic diseases [11]. The importance of calcium influx in mast cell activation and degranulation has been well recognized [12]. The degranulation of mast cell is Ca2+ dependent, and an increase in intracellular Ca2+ characterized by Ca2+ entry through store-operated calcium channels (SOCs) is essential for granule release [13-15]. Multiple mechanisms are involved in regulation of SOCs activity. It has recently been discovered that the two subunits, STIM1 and Orai1, play a vital role in both the signalling and the permeation mechanisms for Ca2+ influx through LDK378 ic50 SOCs. Overexpression of STIM1 together with Orai1 caused a

dramatic increase in store-operated Ca2+ entry in RBL cells [16]. Furthermore, SOC activation has been suggested to be linked to PI-3K signalling pathways, as well as reactive oxygen species (ROS) production, despite controversial. However, whether food allergen–induced mast cell activation is related to the regulation of intracellular Ca2+ signalling, and the underlying mechanism remain unknown. In this study, using Brown-Norway rat food-allergic model, we aimed to investigate the involvement of Ca2+ signalling in food allergen–induced

mast cell activation and degranulation and the underlying mechanisms. We found that Ca2+ entry through SOCs was increased in mast cells in the food-allergic animal model. SOC activation was related to PI3K-ROS-induced upregulation of STIM1 and Orai1 expression. Four-week-old female Brown-Norway rats were purchased from Vital Bacterial neuraminidase River Laboratories (Beijing, China) and housed in groups of four per cage in a controlled environment with a photoperiod of 12-h light/12-h dark and a temperature of 20 ± 2 °C. Sanitary controls were performed for all major rodent pathogens, and the results of these tests were uniformly negative. All the animal experimental procedures were approved by the Animal Care and Use Committee of Shenzhen University and carried out in accordance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication no. 85-23, revised 1996). Forty Brown-Norway rats were randomly divided into two groups: control group and ovalbumin (OVA, Sigma, USA) group.

Cells were maintained in culture for 6 days before their use. After 6 days, human macrophages (hMDMs) were detached by incubation with Accutase (Sigma Aldrich) for 30 min at 37°C and then plated on fibronectin- or Gelatin-FITC-coated coverslips for 24 h in the above medium with a FCS concentration of 1%. Mouse wild-type fibroblasts were isolated from 15–18 days embryos

by standard procedures and SYF (src–/–yes–/–fyn–/–) fibroblasts were learn more obtained from ATCC. Fibroblasts were cultured in DMEM supplemented with 10% FCS, 100 U/mL penicillin, and 100 μg/mL streptomycin. For immunofluorescence experiments, cells were detached with trypsin and then plated for 24 h on fibronectin-coated coverslips in the above medium with a FCS concentration of 1%. Transfection of BMDMs was carried out by electroporation

using the NucleofectorTM technology of Amaxa (Koel, Germany) according to proposed protocols. Cells were transfected with control nonsilencing siRNA pool or mouse-specific ON-TARGET plus siRNA Reagents targeting Abl or Arg (Dharmacon, Lafayette, CO). For fluorescence Selleckchem LDE225 microscopy (confocal analysis of podosome formation) and assays of gelatin degradation, matrigel migration, and trans-endothelial migration, cells were detached after 48 h from transfection and plated on fibronectin- or gelatin-coated coverlips for further 24 h. For assays of migration in 2D and immunoblotting, cells were assayed after 72 h of culture as above described. An aliquot of BMDMs used for the different assays was lysed to control for

the efficacy of Abl silencing by the siRNA-specific reagent. Mean per cent of Abl expression in BMDM Exoribonuclease treated with siRNA targeting Abl was 37.8% ± 11 compared to control siRNA-treated ones. Cells were fixed with 4% (w/v) paraformaldehyde (PFA) for 30 min. PFA was quenched with 50 mM NH4Cl. Cells were then permeabilized with PBS-0.1% Triton X-100, blocked with 1% BSA for 30 min and stained with primary Ab for 1 h. Cells were stained with secondary Ab and rhodamine-phalloidin for 30 min, followed by DAPI (Sigma Aldrich) for 10 min. Images were collected using the SP5 confocal microscope from Leica Microsystems (Wetzlar, Germany) with a 63× objective. Images were processed for brightness and contrast with Adobe Photoshop. Controls were done by staining cells with secondary Abs only or, in the case of Abl, by staining BMDMs in which Abl was silenced with anti-Abl and secondary Abs. In either cases we did nondetect any signal. For gelatin degradation assays, coverslips were incubated with poly-L-Lysine for 20 min, washed with PBS and then incubated with 0.5% glutaraldehyde for 15 min. After washing with PBS, coverslips were put on a drop of 0.2 mg/mL Gelatin-FITC in PBS/2% sucrose, left for 10 min and washed again with PBS. BMDMs and hMDMs were plated for 24 h on gelatin-FITC-coated coverslips.

No typical EEG alterations were observed. Repeated 14-3-3 assay was positive after a first negative test. Neuropathology MAPK inhibitor showed classical CJD changes with small cortical foci of large confluent vacuoles and relatively well-preserved cerebellar cortex. The most striking feature was the presence of abundant Kuru-type plaques in both cerebral cortex and subcortical white matter. Sparse Kuru-type plaques

were also seen in cerebellum, although only in white matter. Immunohistochemistry showed, in addition to unicentric plaques, diffuse synaptic and patchy perivacuolar, as well as plaque-like and periaxonal pathological prion protein deposits (PrPres). Western blot studies demonstrated the co-occurrence of PrPres types 1 and 2 in frontal cortex and a relatively weak type 2 signal in cerebellum. PRNP genotyping revealed methionine homozygosity at codon 129 and excluded mutations. Alisertib This case shows a previously undescribed combination of histopathological features which preclude its classification according to the current phenotypic and molecular sCJD classification.

The observation demonstrates that Kuru-type amyloid plaques mainly involving the cerebral white matter may also occur in sCJD cases with short clinical course and the co-existence of PrPres types 1 and 2. This case further highlights the complexity of the correlations between histopathological phenotype and PrPres isotype

in prion diseases. “
“Mycoplasma pneumoniae is a well-known cause of atypical pneumonia. CNS involvement is a relatively frequent extrapulmonary manifestation, most commonly manifesting as encephalitis in the pediatric population. We present two unusual cases Janus kinase (JAK) of M. pneumoniae encephalitis that presented with symptoms and imaging findings suggesting mass occupying lesions, and worsening altered mental status. Biopsy of the lesions was necessary in both cases to aid with diagnosis. Histopathologic features excluded neoplasm, and established the diagnosis of encephalitis, but did not point toward its etiology. The only finding that indicated M. pneumoniae as the most likely pathogen was serum IgM positivity in the absence of any other identifiable infectious source, and complete neurologic recovery following specific anti-mycoplasmal treatment. The patients were successfully treated with antibiotics and steroids, with the second case also requiring intravenous immunoglobulin and anti-epileptics. The clinical presentation and histopathologic findings suggested an immune-mediated pathogenesis, but acute disseminated encephalomyelitis was excluded due to extensive gray matter involvement. Disease resolution despite status epilepticus and herniation in case 2 is a novel finding of the study.

Additionally, more investigation is needed to define how HSV-2 infection might modulate HIV-1 pathology. Support for this work was provided by the National Institute of Allergies and Infectious Diseases (grants NIAID AI060379, AI052731 and AI064520 to DFN and AI64520 to LLL). JDB is supported by

AI-066917 and AI-076014 (NIAID). Additional support was provided by the Brazilian Program for STD and AIDS, Ministry of Health (914/BRA/3014 – UNESCO/Kallas), the São Paulo City Health Department (2004-0·168·922-7/Kallas), Fundação de Amparo a Pesquisa do Estado de São Paulo (04/15 856-9/Kallas), Panobinostat cell line the John E. Fogarty International Center (D43 TW00003) and the AIDS Research Institute of the AIDS Biology Program at UCSF (grant to DFN). MMS and KIC’s scholarships were supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazilian Ministry of Education. LLL is an American Cancer Society

Research Professor. We thank Skip Virgin for helpful discussions. The authors declare no conflict of interest. “
“Citation Petroff MG, Perchellet A. B7 family molecules as regulators of the maternal immune system in pregnancy. Am J Reprod Immunol 2010 Placental and fetal growth and development are associated with chronic exposure of the maternal immune system to fetally derived, paternally inherited antigens. Because maternal lymphocytes are aware of fetal buy ICG-001 antigens, active tolerance mechanisms are required selleck chemicals to ensure unperturbed progression of pregnancy and delivery of

a healthy newborn. These mechanisms of tolerance may include deletion, receptor downregulation, and anergy of fetal antigen-specific cells in lymphoid tissues, as well as regulation at the maternal–fetal interface by a variety of locally expressed immunoregulatory molecules. The B7 family of costimulatory molecules comprises one group of immunoregulatory molecules present in the decidua and placenta. B7 family members mediate both inhibitory and stimulatory effects on T-cell activation and effector functions and may play a critical role in maintaining tolerance to the fetus. Here, we review the known functions of the B7 family proteins in pregnancy. Placental and fetal growth and development are associated with chronic exposure of fetally-derived, paternally inherited antigens to the maternal immune system. Based on studies in mice, this exposure to paternal antigens is thought to occur as early as insemination, wanes until establishment of the fully mature placenta, and again becomes robust when the uterine blood supply to the placenta is established.1–3 Once this occurs, the placenta is inundated with maternal blood, and antigen efflux from the fetus persists for the last 1/2 of pregnancy in mice, and 2/3 of pregnancy in women. In women, the continuous shedding of trophoblast cells and other soluble fetal products is thought to be a major source of antigen to maternal immune cells.

(p. 287) I can think of no better term than “awesome” to describe the excitement and vibrancy of our field. This article is a revised version of a presidential address delivered on June 8, 2012 at the biennial meeting of the International Society on Infant Studies, held in Minneapolis, MN. I am indebted to the many faculty mentors, collaborators, postdoctoral fellows, Talazoparib supplier and graduate students who have filled my head with ideas and implemented

those ideas in ways that I never dreamed possible. Grant support was provided by NIH research grants HD-037086 to RNA and Elissa Newport, HD-073890 to Michael Tanenhaus and RNA, and HD-067250 to Daniel Weiss and RNA. “
“We conducted two experiments to address questions over whether 9-month-old this website infants believe that objects depicted in realistic photographs can be picked up. In Experiment

1, we presented 9-month-old infants with realistic color photographs of objects, colored outlines of objects, abstract colored “blobs,” and blank pages. Infants most commonly rubbed or patted depictions of all types. They also showed significantly more grasps toward the realistic photographs than toward the colored outlines, blobs, and blank pages, but only 24% of infants directed grasping exclusively at the photographs. In Experiment 2, we further explored

infants’ actions toward objects and pictures while controlling for tactile information. We presented 9-month-old infants with objects and pictures of objects under a glass cover in a false-bottom table. Although there were no significant differences between the proportion of rubs and pats infants directed toward the objects versus the photographs, infants exhibited significantly more grasping toward the objects than the photographs. Together, these findings show that 9-month-old infants largely direct appropriate actions toward realistic photographs and real objects, indicating that they perceive different affordances for pictures and objects. “
“This Thymidylate synthase study explores the relationship between tonal synchrony and maternal-infant social engagement based on free-play recordings of 15 mothers and their 3-month-old infants in a laboratory setting. Moment-by-moment analyses on a microlevel were used to study social engagement and vocal interaction. We analysed and categorized 854 vocalization periods (mother-only vocalizations, tonal interaction periods, nontonal interaction periods, and mutual silence). Tonal synchrony was analysed in terms of harmonic and pentatonic series based on pitch frequency analyses. Social engagement was microanalyzed in terms of matched and mismatched engagement states.

iTreg cells were generated as previously described by Vaeth et al. [26]. The DNA was isolated and analysed for methylation of the TSDR region. No differences in the methylation rate were detectable in Foxp3+ aTreg cells generated under the different experimental conditions (Fig. 3E). Foxp3+ Treg cells, isolated from all four cultures, revealed almost 100%

demethylation Sotrastaurin order of the TSDR region whereas the TSDR of the Teff cells was completely methylated. As expected, the TSDR of GFP+iTreg cells was still up to 60% methylated as indicated by the colour-coded matrix. We therefore assume again that the Foxp3+ cells detectable in our cultures are expanded nTreg cells. Next, we rechallenged isolated CD4+CD25+ cells with CD19+ allogeneic B cells. The Foxp3 frequency was determined on day 0 and 4 of restimulation culture. Restimulation

cultures of aTreg cells generated with aCD4, aCD4+Rapa or untreated cultures resulted in reduced frequencies GSK2118436 of Foxp3+ Treg cells (Fig. 3F). Only aCD4+TGF-β+RA aTreg cells displayed a stable Foxp3 frequency and even slightly increased in numbers upon restimulation. We tested the suppressive capacity of our in vitro generated aTreg cells in an acute GvHD (aGvHD) model. In summary, aTreg cells were generated as described above under aCD4- mAb mono-therapy or addition of TGF-β+RA or Rapa. On day 7 of primary culture, either aTreg cells or freshly isolated nTreg cells were enriched. A total of 2 × 105 C57BL/6 Treg cells were injected into myeloablatively irradiated BALB/c recipients together with 5 × 106 C57BL/6 BM cells. Two days after Niclosamide Treg-cell transfer, the mice were challenged with 1 × 106 CD4+/CD8+ C57BL/6 T cells from LUC

transgenic animals as previously described [27]. To visualise the distribution of the allogeneic effector T cells (Teff) and progress of aGvHD, the mice were monitored with bioluminescence imaging and for weight changes as a parameter of disease manifestation (Fig. 4A). Using this stringent model with a very low Treg to Teff ratio (1:5), transferred nTreg cells were unable to ameliorate aGvHD and to prolong survival (Fig. 4C and D). aTreg cells generated by aCD4 monotherapy or by addition of Rapa or TGF-β+RA prevented expansion of LUC transgenic effector T cells quantified with BLI, in contrast to controls (only transplantation of BM cells and effector T cells), mice that received aTreg cells from untreated culture conditions, or mice that had received nTreg cells in which LUC transgenic effector T cells massively infiltrated lymph nodes (LNs) and the intestinal tract (Fig. 4B and C). Improved survival after allogeneic BM transplantation further corroborated the in vivo effectiveness of the generated aTreg cells (Fig. 4D).

A few research groups have adapted clinical DENV isolates to the murine host to obtain adapted strains that are able to induce disease resembling human infection. Atrasheuskaya et al.[63] showed that young BALB/c mice (4-weeks old) were found to be sensitive selleck inhibitor to the challenge with a

mouse-adapted DENV-2 (strain P23085, GenBank: AY927231.1). They developed clinical manifestations such as arching of the back, ruffling of the fur and slowing of activity. The presence of DENV-2 virus in the blood was confirmed by RT-PCR and mice showed severe weight loss ending in limb paralysis and 100% mortality. The most important changes in production of pro-inflammatory markers were seen in TNF-α, which quickly increased 24 hr before death. This model supports the notion that activation of the innate immune response is partially responsible for mortality in DENV-2 virus infection. In line with this hypothesis, anti-TNF-α treatment significantly reduced the mortality rates.[63] Similarly, BALB/c mice-infected intraperitoneally with a DENV-2 isolate demonstrated liver damage, as determined by high AST and ALT levels that peaked at day Trichostatin A in vitro 7 post-infection.[64]

Our group described a DENV infection model in adult BALB/c or C57BL/6 mice (≥ 8 weeks old), using the mouse-adapted DENV-2 strain (P23085), from Atrasheuskaya et al.[63] The adapted virus given systemically (intraperitoneally) induced inoculum-dependent lethality that was preceded by major manifestations of severe DENV infection in humans such as mechanical hypernociception (an index of pain), thrombocytopenia, haemoconcentration, increased vascular permeability, hypotension, increased levels of cytokines and chemokines, tissue haemorrhage, viraemia and recovery of viral load in target organs of infection.[65-71] Viral replication and lethality were abolished after in vitro or in vivo neutralization using the anti-DENV-2 monoclonal antibody 4G2.[68] Moreover, the adapted DENV-2 strain was not found in the brain of intraperitoneally infected mice.[71] This model of DENV-2 infection in immune competent

mice provides an important tool to study host–virus interactions and mechanisms associated with severe disease manifestation, so contributing to the elucidation of 4��8C DENV pathogenesis.[65, 67-70] However, a possible drawback of the model is that it uses a single strain that was adapted by multiple passages in mice. All eventual modifications of the virus to the murine host are currently under investigation because they may cause a disease that is significantly different to that of the original virus in humans.[19] Table 1 summarizes the most studied mouse models of dengue infection available in the literature. Mice develop functional human immune system, including adaptive immunity; infection of human cells lineages; study of ‘human’ response to infection.

To our knowledge, such detailed description of bone intragraft chimerism has not been accomplished before. These methods can be applied in future research to study the effect of transplant enhancement techniques or various immunosuppressive regimens

on intragraft chimerism. Pelzer et al. determined the overall lineage of cells in transplants treated with short-term immunosuppression and donor-derived neoangiogenesis.[15] Their PF-6463922 supplier study describes the effect of short-term immunosuppression (2 weeks), resulting in a lower percentage of cells of recipient lineage present in the donor transplant in short-term immunosuppressed rats as compared to non-immunosuppressed rats, due to protection of donor cells from rejection. In this study, therefore, a higher rER would be expected in allotransplants if no immunosuppression was administered leading to increased rejection of donor cells. Conversely, a lower rER might be expected if even longer term immunosuppression was used. With intramedullary arteriovenous bundle implantation,

the rER increases, likely due to a higher supply of recipient-derived bone forming cells and increased immunogenic exposure resulting in donor cell death and a relatively higher amount of recipient selleck inhibitor cells present.[15] In this study, we describe the progress of intragraft chimerism within specific areas and compare this with cell lineage as it would occur in autogenous transplantation. The fact that the allotransplant is repopulated rapidly with

almost half of the cells of recipient origin at 4 weeks, increasing to 3/4th of the recipient cells at 18 weeks, proves that intragraft chimerism is a rapid process in vascularized allotransplants. This extend of chimerism at 18 weeks was also found by Pelzer et al., who describes 81% of bone cells in immunosuppressed allotransplants to be recipient derived at 18 weeks.[15] Equally, Muramatsu et al. determined allotransplant cell lineage in rats with semiquantitative PCR techniques and found that by 24 weeks approximately 90% of fresh allotransplant bone had been repopulated by recipient cells.[17] Despite the dimensional differences between rat and human bone, the rate of bone remodeling Methamphetamine has been found to be comparable between rodent and human bone.[18] Therefore, these high rates of transplant chimerism could be translated to human bone transplant biology. In this study, a short-term (2 weeks) course of Tacrolimus was administered since the combined use of 2 weeks immunosuppression with donor-derived neoangiogenesis has proven to sustain bone blood flow and bone transplant viability long term.[10, 19] This may be explained in part by the neoangiogenic circulation and resulting influx of donor-derived cells repopulating the bone. After the initial 2-week immunosuppression, immune competence also gradually improves.