CT volumetry helps predict prognosis of large hepatocellular carcinoma after resection.

AIM: To determine whether the tumour volume measurement on preoperative contrast-enhanced computed tomography (CT) could be used to predict the overall survival patients with large hepatocellular carcinoma (>5 cm) after resection. MATERIALS AND METHODS: This study included 171 patients with surgically confirmed hepatocellular carcinoma who underwent preoperative CT. The largest diameter, the product of the axial dimension, tumour volume, and tumour-to-liver volume ratio (TTLVR) on CT images were measured and calculated. The univariate and multivariate Cox proportional hazard ratio regression models were used to identify the impact of the tumour burden-related risk factors on overall survival. RESULTS: In multivariate analysis, TTLVR (p=0.042) and major vascular invasion (p=0.006) were independently associated with overall survival of patients with hepatocellular carcinoma after the resection. The group in which the patients had a low TTLVR showed higher cumulative survival rates than patients with a TTLVR (p=0.004). Patients with a low TTLVR (≤26.23%) and absence of major vascular invasion had significantly higher cumulative survival rates compared to those patients with hepatocellular carcinoma with either or both the risk factors (p=0.001). CONCLUSION: A higher TTLVR in combination with the presence of major vascular invasion was associated with poorer overall survival in patients with large hepatocellular carcinoma after resection.

Thermophoretic collection of virus-laden (SARS-CoV-2) aerosols.

Detecting the existence of SARS-CoV-2 in the indoor atmosphere is a practical solution to track the prevalence and prevent the spread of the virus. In this work, a thermophoretic approach is presented to collect the novel coronavirus-laden aerosols from the air and accumulate to high concentrations adequate for the sensitivity of viral RNA detection. Among the factors, the density and particle size have negligible effects on particle trajectory, while the vertical coordinates of particles increase with the rise in heating source temperature. When the heating temperature is higher than 355 K , all of the particles exit the channel from one outlet; thus, the collecting and accumulating of virus-laden aerosols can be realized. This study provides a potential approach to accelerate the detection of SARS-CoV-2 and avoid a false negative in the following RNA test.

Cells with ganglionic differentiation frequently stain for VE1 antibody: a potential pitfall.

Mitogen-activated protein kinase (MAPK) pathway plays a major role in pediatric low-grade gliomas (pLGGs). Immunohistochemistry with mutant-specific antibody, VE1, has appeared to be the most affordable and rapidly deployable method to identify tumors with aberrant MAPK signaling pathway, by highlighting tumor with BRAFV600E mutation. Nonetheless, positive staining cases but not associated with BRAFV600E mutation are also seen. We analyzed 62 pLGGs for the two commonest genetic aberrations in MAPK pathway: KIAA1549-BRAF fusion, using reverse-transcriptase polymerase chain reaction, and BRAFV600E mutation, using VE1 antibody and Sanger sequencing. We recorded a specificity and accuracy rate of 68.75% and 75%, respectively, for VE1, when strong cytoplasmic staining is observed. Interestingly, we observed that cells with ganglionic features frequently bind VE1 but not associated with BRAFV600E mutation. Such observation was also confirmed in four cases of differentiating neuroblastoma. This false positive staining may serve as an important confounder in the interpretation of VE1 immunoreactivity with major therapeutic implication. It is important to confirm the presence of BRAFV600E mutation by DNA-based method, especially in tumor entities not known to, or rarely harbor such mutations.

Effect of patchouli alcohol on macrophage mediated Helicobacter pylori digestion based on intracellular urease inhibition.

BACKGROUND: Helicobacter pylori infects almost half of the world population and is listed as a type I carcinoma factor since 1994. Pogostemon cablin (Blanco) Benth. (Labiatae) has been used to treat gastro-intestinal diseases for thousands of years in many east Asian countries, and the key ingredient, patchouli alcohol (PA), has been observed to exert anti-H. pylori and anti-urease activities. PURPOSE: We investigated the effect of PA on H. pylori urease and its subsequent influence on macrophage phagosome maturation and function. METHODS: In H. pylori experiment, the berthelot method and pH shock assay were adopted to evaluate the effect of PA on extracellular and intracellular H. pylori urease. And then, Q-PCR and Western blot were carried out to analyze the alterations in the expression of urease-related genes and proteins after PA treatment. In the H. pylori and macrophage cell (RAW264.7) co-culture experiment, the effects of PA on H. pylori-induced phagocytosis and intracellular killing of RAW264.7 were investigated using gentamycin protection assay, and the underlying mechanism was explored by immunofluorescence. RESULTS: PA at 25 and 50 µM inhibited intracellular H. pylori urease activity but not isolated urease by down-regulating the gene expression levels of ureB, ureE, ureI and nixA and reducing the protein expression level of UreB, thereby inhibiting the acid resistance of H. pylori. PA also recovered the function of macrophage bacterial digestion, and prior treatment with ammonium chloride inhibited the efficacy of PA. CONCLUSION: PA suppressed intracellular H. pylori urease function and maturation, which increased macrophage digestion ability.

[HIV prevalence and correlated factors on male clients of female sex workers in Hekou Yao autonomous county of Yunnan province, 2014-2015].

Objective: To assess the prevalence and related factors of HIV infection among male clients of the female sex workers in Hekou Yao autonomous county of Honghe Hani Yi autonomous prefecture (Hekou county) in Yunnan province in China, 2014-2015. Methods: Serial cross-sectional survey was conducted during June 2014 to November 2015. Convenience sampling methods were used to recruit the male clients for this study. Self-reported information on social-demographic characteristics, with sexual and drug behavior patterns, was gathered. Both blood and urine samples were collected for HIV, with for opiate testing. Multivariate logistic regression and Exhaustive CHAID method were used to determine the correlated factors associated with HIV infection. Statistical analysis was used by SPSS 22.0 software and Clementine 12.0 software. Results: The overall HIV prevalence of male clients was 2.06% (16/776). Male clients who keep using condom with female sex worker was estimated as 68.81% (534/776). The last commercial sexual partner of Vietnamese male clients was all Vietnamese female sex workers. Compared with Chinese male clients, Vietnamese male clients have a higher rate of morphine positive. Factors as: age ≥50 years vs. age <30 years (OR=8.11, 95%CI: 1.26-52.16) and testing for morphine positive vs. morphine negative (OR=7.35, 95%CI: 1.42-38.06) were significantly associated with HIV infection through multiple logistic regression analysis. Through Exhaustive CHAID, it confirmed that age was the primary factor that associated with HIV infection of male clients. Conclusions: Relationship between morphine and HIV infection indicated that HIV prevalence of male clients in Hekou county was influenced by the combined effect of both illegal drug use and commercial sexual behavior. Special attention should be paid to male clients over 50 years of age, on HIV intervention.

Long non-coding RNA CRNDE is a novel tumor promoter by modulating PI3K/AKT signal pathways in human gastric cancer.

OBJECTIVE: Long non-coding RNA CRNDE (CRNDE) recently emerged as a carcinogenic promoter in various cancers including gastric cancer (GC). However, the functions and molecular mechanisms of CRNDE to GC are still largely unclear. The aim of this study was to investigate the clinical significance and functional mechanisms of CRNDE expression in GC. PATIENTS AND METHODS: The expression of CRNDE was detected by quantitative Real-time PCR (qRT-PCR) in GC specimens and cell lines. The correlation between the CRNDE expression and clinicopathological parameters was investigated. Survival rate was determined with Kaplan-Meier and statistically analyzed with the log-rank method between groups. Subsequently, the significance of survival variables was analyzed using the Cox multivariate proportional hazards model. Then, MTT and Transwell assays were used to assess cell proliferation, migration and invasion capacity. Finally, Western blot analysis was performed to explore the effects of CRNDE knockdown on the PI3K/Akt pathway. RESULTS: We observed that expression of CRNDE was higher in GC tissues and cells compared with the normal gastric tissue and normal gastric cell lines. High expression of CRNDE was correlated with invasion depth (p = 0.006), TNM stage (p = 0.010) and lymph node metastasis (p = 0.005). Furthermore, high CRNDE expression was associated with shorter overall survival (p = 0.0066) of GC patients. Multivariate analysis confirmed that high CRNDE expression was a significant independent predictor of poor survival in GC. In vitro assay indicated that knockdown of CRNDE inhibited cell proliferation, migration and invasion of GC. Finally, the data of Western blot showed that CRNDE exerted its oncogenic role by affecting PI3K/AKT signaling pathways. CONCLUSIONS: Our findings indicate that CRNDE plays an important role in promoting GC progression and may represent a novel prognostic biomarker in GC.

In Vitro and In Vivo Antibacterial Activities of Patchouli Alcohol, a Naturally Occurring Tricyclic Sesquiterpene, against Helicobacter pylori Infection.

This study further evaluated the in vitro and in vivo anti-Helicobacter pylori activities and potential underlying mechanism of patchouli alcohol (PA), a tricyclic sesquiterpene. In the in vitro assay, the capacities of PA to inhibit and kill H. pylori were tested on three standard strains at different pH values and on 12 clinical isolates. The effects of PA on H. pylori adhesion (and its alpA, alpB, and babA genes), motility (and its flaA and flaB genes), ultrastructure, and flagellation were investigated. Moreover, the H. pylori resistance to and postantibiotic effect (PAE) of PA were determined. Furthermore, the in vivo effects of PA on H. pylori eradication and gastritis were examined. Results showed that MICs of PA against three standard strains (pH 5.3 to 9) and 12 clinical isolates were 25 to 75 and 12.5 to 50 µg/ml, respectively. The killing kinetics of PA were time and concentration dependent, and its minimal bactericidal concentrations (MBCs) were 25 to 75 µg/ml. In addition, H. pylori adhesion, motility, ultrastructure, and flagellation were significantly suppressed. PA also remarkably inhibited the expression of adhesion genes (alpA and alpB) and motility genes (flaA and flaB). Furthermore, PA treatment caused a longer PAE and less bacterial resistance than clarithromycin and metronidazole. The in vivo study showed that PA can effectively eradicate H. pylori, inhibit gastritis, and suppress the expression of inflammatory mediators (COX-2, interleukin 1ß, tumor necrosis factor alpha, and inducible nitric oxide synthase [iNOS]). In conclusion, PA can efficiently kill H. pylori, interfere with its infection process, and attenuate gastritis with less bacterial resistance, making it a potential candidate for new drug development.

Hydrogen Sulfide Protects Renal Grafts Against Prolonged Cold Ischemia-Reperfusion Injury via Specific Mitochondrial Actions.

Ischemia-reperfusion injury is unavoidably caused by loss and subsequent restoration of blood flow during organ procurement, and prolonged ischemia-reperfusion injury IRI results in increased rates of delayed graft function and early graft loss. The endogenously produced gasotransmitter, hydrogen sulfide (H2 S), is a novel molecule that mitigates hypoxic tissue injury. The current study investigates the protective mitochondrial effects of H2 S during in vivo cold storage and subsequent renal transplantation (RTx) and in vitro cold hypoxic renal injury. Donor allografts from Brown Norway rats treated with University of Wisconsin (UW) solution + H2 S (150 µM NaSH) during prolonged (24-h) cold (4°C) storage exhibited significantly (p < 0.05) decreased acute necrotic/apoptotic injury and significantly (p < 0.05) improved function and recipient Lewis rat survival compared to UW solution alone. Treatment of rat kidney epithelial cells (NRK-52E) with the mitochondrial-targeted H2 S donor, AP39, during in vitro cold hypoxic injury improved the protective capacity of H2 S >1000-fold compared to similar levels of the nonspecific H2 S donor, GYY4137 and also improved syngraft function and survival following prolonged cold storage compared to UW solution. H2 S treatment mitigates cold IRI-associated renal injury via mitochondrial actions and could represent a novel therapeutic strategy to minimize the detrimental clinical outcomes of prolonged cold IRI during RTx.

Long non-coding RNA MALAT1 is an independent prognostic factor of osteosarcoma.

OBJECTIVE: Accumulating evidence revealed that long non-coding RNAs (lncRNAs) were emerging regulators in cancer biology, and could be used as potential biomarkers for cancer prognosis. In this study, we focused on MALAT1 and investigated its expression pattern, clinical significance in osteosarcoma. PATIENTS AND METHODS: The expression of lncRNA MALAT1 was analyzed in 162 osteosarcoma tissues by quantitative real-time PCR (qRT-PCR). Then, we explored the potential relationship between MALAT1 expression levels in tumor tissues and clinicopathological features of osteosarcoma, and clinical outcome. RESULTS: We found that which was significantly up-regulated in osteosarcoma tissues compared with paired non-tumor tissues (p < 0.01). The expression of MALAT1 was remarkably associated with advanced clinical stage and distant metastasis of osteosarcoma patients (p < 0.05). The Kaplan-Meier survival analysis showed that osteosarcoma patients with higher levels of MALAT1 had a shorter survival time. The multivariate Cox regression analysis demonstrated that MALAT1 expression level was an independent prognostic factor for the overall survival rate of osteosarcoma patients. CONCLUSIONS: Our results demonstrated the clinical prognostic significance and roles of MALAT1 in osteosarcoma, and suggested that MALAT1 may be considered as a prognostic biomarker and therapeutic target for osteosarcoma.

MicroRNA-1908 is a biomarker for poor prognosis in human osteosarcoma.

OBJECTIVE: The aim of the present study was to analyze microRNA-1908 expression in human osteosarcoma and to explore the potential of miRNAs as biomarkers for patient outcomes. PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction assay was performed to evaluate the expression level of microRNA-1908 in 212 patients diagnosed osteosarcoma. The association of miR-1908 expression with clinicopathological factors or the prognosis of glioma patients were also analyzed. Furthermore, the Kaplan-Meier method and Cox's proportional hazards model was used to determine survival rate. RESULTS: MiR-1908 expression levels in osteosarcoma tissues were significantly higher than those in matched adjacent normal bone tissues (p < 0.001). Tumors with high miR-1908 expression had significantly greater extent of recurrence (p < 0.003), metastasis (p = 0.000), and chemotherapy response (p < 0.019) than those with low miR-1908 expression. Kaplan-Meier analysis showed that patients with low level of miR-1908 had favorable trends of survival (p < 0.001). The result of the multivariate analysis showed that miR-1908 expression level and metastasis status retained significance as an independent prognostic factor of human osteosarcoma. CONCLUSIONS: Our study demonstrates that increased microRNA-1908 expression is associated with poor clinical outcome in human osteosarcoma.

RIPK3-mediated necroptosis regulates cardiac allograft rejection.

Cell death results in tissue damage and ultimately donor graft rejection and can occur as an active molecular process through apoptotic, necrotic and newly identified receptor interacting protein 1 and 3 kinase (RIPK1/3)-mediated necroptotic pathways. Necroptosis leads to the release of inflammatory molecules which can activate host immune cells. This pathway has yet to be studied in heart transplantation. We have found that necroptosis was induced in murine cardiac microvascular endothelial cell (MVEC) under anti-apoptotic condition following tumor necrosis factor alpha treatment. Necroptotic cell death and release of the danger molecule high mobility group box 1 (HMGB1) were inhibited by the RIPK1 inhibiting molecule necrostatin-1 and by genetic deletion of RIPK3. In addition, tissue necrosis, release of HMGB1 and graft cell infiltrate were attenuated in RIPK3 null heart allografts following transplantation. Finally, a brief sirolimus treatment markedly prolonged RIPK3 null cardiac allograft survival in allogeneic BALB/c recipients as compared to WT C57BL/6 donor grafts (95 ± 5.8 vs. 24 ± 2.6 days, p < 0.05). This study has demonstrated that RIPK1/3 contributes to MVEC death and cardiac allograft survival through necroptotic death and the release of danger molecules. Our results suggest that targeting RIPK-mediated necroptosis may be an important therapeutic strategy in transplantation.

Spi6 protects alloreactive CD4(+) but not CD8 (+) memory T cell from granzyme B attack by double-negative T regulatory cell.

Memory T (Tm) cells pose a major barrier to long-term transplant survival. Whether regulatory T cells (Tregs)can control them remains poorly defined. Previously,we established that double-negative (DN) Tregs suppress effector T (Teff) cells. Here, we demonstrate that DNTregs effectively suppress CD4+/CD8+Teff and CD8+Tm but not CD4+Tm cells, whereas the suppression on CD8+Tm is abrogated by perforin (PFN) deficiency in DNTregs. Consistently, in a BALB/c to B6-Rag1-/-skin transplantation, transfer of DN Tregs suppressed the rejection mediated by CD4þ/CD8+Teff and CD8+Tmcells (76.0±4.9, 87.5±5.0 and 63.0±4.7 days, respectively)but not CD4þTmcells (25.3±1.4 days). Both CD8þ effector memory T and central memory T compartments significantly reduced after DN Treg transfer. CD4+Tm highly expresses granzyme B (GzmB) inhibitor serine protease inhibitor-6 (Spi6). Spi6 deficiency renders CD4þTm susceptible to DN Treg suppression. In addition,transfer of WT DN Tregs, but not PFN-/-DN Tregs,inhibited the skin allograft rejection mediated by Spi6-/-CD4þTm(75.5±7.9 days). In conclusion, CD4+ and CD8+Tm cells differentially respond toDNTregs' suppression.The GzmB resistance conferred by Spi6 in CD4þTm cells might hint at the physiological significance of Tmpersistence

Induction of alloimmune tolerance in heart transplantation through gene silencing of TLR adaptors.

Toll-like receptors (TLRs) activate biochemical pathways that evoke activation of innate immunity, which leads to dendritic cell (DC) maturation and initiation of adaptive immune responses that provoke allograft rejection. We aimed to prolong allograft survival by selectively inhibiting expression of the common adaptors of TLR signaling, namely MyD88 and TRIF, using siRNA. In vitro we demonstrated that blocking expression of MyD88 and TRIF led to reduced DC maturation. In vivo treatment of recipients with MyD88 and TRIF siRNA significantly prolonged allograft survival in the BALB/c > C57BL6 cardiac transplant model. Moreover, the combination of MyD88 and TRIF siRNA along with a low dose of rapamycin further extended the allograft survival (88.8 ± 7.1 days). Tissue histopathology demonstrated an overall reduction in lymphocyte interstitium infiltration, vascular obstruction and hemorrhage in mice treated with MyD88 and TRIF siRNA vector plus rapamycin. Furthermore, treatment was associated with an increase in the numbers of CD4(+) CD25(+) FoxP3(+) regulatory T cells and Th2 deviation. To our knowledge, this study is the first demonstration of prolonging the survival of allogeneic heart grafts through gene silencing of TLR signaling adaptors, highlighting the therapeutic potential of siRNA in clinical transplantation.

Regulatory T cells are critical to tolerance induction in presensitized mouse transplant recipients through targeting memory T cells.

Memory T cells are a significant barrier to induction of transplant tolerance. However, reliable means to target alloreactive memory T cells have remained elusive. In this study, presensitization of BALB/c mice with C57BL/6 skin grafts generated a large number of OX40(+)CD44(hi)effector/memory T cells and resulted in rapid rejection of donor heart allografts. Recognizing that anti-OX40L monoclonal antibody (mAb) (alpha-OX40L) monotherapy prolonged graft survival through inhibition and apoptosis of memory T cells in presensitized recipients, alpha-OX40L was added to the combined treatment protocol of LF15-0195 (LF) and anti-CD45RB (alpha-CD45RB) mAb-a protocol that induced heart allograft tolerance in non-presensitized recipients but failed to induce tolerance in presensitized recipients. Interestingly, this triple therapy restored donor-specific heart allograft tolerance in our presensitized model that was associated with induction of tolerogenic dendritic cells and CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs). Of note, CD25(+) T cell depletion in triple therapy recipients prevented establishment of allograft tolerance. In addition, adoptive transfer of donor-primed effector/memory T cells into tolerant recipients markedly reduced levels of Tregs and broke tolerance. Our findings indicated that targeting memory T cells, by blocking OX40 costimulation in presensitized recipients was very important to expansion of Tregs, which proved critical to development of tolerance.

Malignant perivascular epithelioid cell tumour of the fibula: a report and a short review of bone perivascular epithelioid cell tumour.

Perivascular epithelioid cell tumour (PEComa) is a term applied to a family of mesenchymal tumours composed of varying proportions of spindle and epithelioid cell components associated with HMB-45 expression. PEComa rarely arises in the soft tissue, visceral organs, skin and bone. This report details an instance when a purely epithelioid PEComa arose from the right fibula of a 52-year-old Chinese woman without features of tuberous sclerosis complex. The excision specimen disclosed an epithelioid tumour with a nested pattern associated with areas of nuclear pleomorphism, mitotic activity, necrosis and vascular invasion in addition to HMB-45 expression on immunohistochemistry. To the best of the authors' knowledge, this represents the first case of a histologically malignant PEComa of the bone. A short review of primary bone PEComas and potential problems in diagnosis is presented.

Beta-escin, a natural triterpenoid saponin from Chinese horse chestnut seeds, depresses HL-60 human leukaemia cell proliferation and induces apoptosis.

Beta-escin, a natural triterpenoid saponin isolated from the seed of the horse chestnut, is known to generate a wide variety of biochemical and pharmacological effects. The purpose of the present study was to examine the apoptotic and antiproliferative activity of beta-escin in HL-60 human acute myeloid leukaemia cells. Antiproliferative activity was examined by soft agar colony assay and the trypan blue exclusion method. Apoptotic activity was evaluated by morphological analysis, annexin V analysis, DNA fragmentation analysis and flow cytometry cell cycle analysis. The results showed that beta-escin caused a significant inhibition of HL-60 cell proliferation in a dose- and time-dependent manner. Morphological evidence of apoptosis, including vacuolization, apoptotic nuclei fragmentation and apoptotic body formation, was observed in cells treated with 30 microg mL(-1) of beta-escin for 24, 48 and 72 h. A significant increase in the population of annexin V+ and PI- cells (early apoptotic) among the total cells was observed in cells treated with beta-escin (30-50 microg mL(-1)) for 24 h (P<0.001). Typical DNA ladders, DNA with a unit length of about 180 bp, were detected in cells treated with beta-escin (30-50 microg mL(-1)) for 48 h by agarose gel electrophoresis. Flow cytometry cell cycle analysis revealed that beta-escin (30-50 microg mL(-1)) induced G1-S arrest and led to a significant accumulation of the sub-G1 population in HL-60 cells (P<0.05). Taken together, the results demonstrate that beta-escin is a potent natural inhibitor of cell proliferation and inducer of apoptosis in HL-60 acute myeloid leukaemia cells. The results indicate that beta-escin may be a useful candidate agent for exploring potential antileukaemic drugs.

RIP2 is required for NOD signaling but not for Th1 cell differentiation and cellular allograft rejection.

Two previous reports that receptor-interacting protein (RIP)-2 knockout (RIP2-/-) mice had defective nuclear factor-kappa B (NF-kappaB) signaling and T helper (Th)1 immune responses had led us to believe that this putative serine-threonine kinase might be a possible target for transplant immunosuppression. Thus, we tested whether RIP2-/- mice were able to reject vascularized allografts. Surprisingly, we found that T cells from RIP2-/- mice proliferated and produced interferon (IFN)-gamma after allostimulation in vitro. Moreover, naïve RIP2-/- CD4+ T cells differentiated normally into Th1 or Th2 cells under appropriate cytokine microenvironments. Consistent with these findings, no difference in allograft survival was observed between wild-type and RIP2-/- recipient mice, and rejection had similar pathology and cytokine profiles in both types of recipients. RIP2 deficiency was associated with defective NOD signaling, but this did not affect T-cell receptor (TCR)-dependent activation of the canonical NF-kappaB signaling or expression of NF-kappaB genes in rejecting allografts. Our data demonstrate that RIP2-deficient mice have intact canonical NF-kappaB signaling and can mount Th1-mediated alloresponses and reject vascularized allografts as efficiently as wild-type mice, thus arguing against RIP2 as a primary target for immunosuppression.

Prolongation of allograft survival by administration of anti-CD45RB monoclonal antibody is due to alteration of CD45RBhi: CD45RBlo T-cell proportions.

CD45RB monoclonal antibody (mAb) therapy is capable of prolonging allograft survival. We have previously shown that CD45RB mAb enriches the CD45RBlo T-cell population in vitro and in vivo by preferentially depleting CD45RBhi T cells. The present study assessed the importance of CD45RBhi T-cell depletion in murine cardiac allograft survival by infusion of naive CD45RB T-cell subsets. Here we show that naturally occurring CD45RBloCD4+ T cells express regulatory transcription factor Foxp3 and have regulatory function, whereas CD45RBhiCD4+ T cells express low levels of Foxp3 and have effector function. Infusion of syngeneic CD45RBhi T cells significantly reduced graft survival after depletion of CD45RBhi T cells by CD45RB mAb. Reduction of graft survival also occurred when syngeneic CD45RBhi T cells were infused into rapamycin-treated mice, whereas survival was prolonged when CD45RBlo T cells were added. This indicates that an alteration in the balance between regulatory CD45RBlo and effector CD45RBhi T cells is critical to the immunologic function of CD45RB mAb. A strategy to eliminate effector T cells with consequent enrichment of the regulatory T-cell compartment may be an important new strategy in the prevention of rejection.