In vitro assessment of electrospun polyamide-6 scaffolds for esophageal tissue engineering.

Artificial tissue-engineered grafts offer a potential alternative to autologous tissue grafts for patients, which can be traumatic. After decellularizing Papio hamadryas esophagus and studying the morphology and physical properties of the extracellular matrix (ECM), we generated electrospun polyamide-6 based scaffolds to mimic it. The scaffolds supported a greater mechanical load than the native ECM and demonstrated similar 3D microstructure, with randomly aligned fibers, 90% porosity, 29 µm maximal pore size, and average fiber diameter of 2.87 ± 0.95 µm. Biocompatibility studies showed that human adipose- and bone marrow-derived mesenchymal stromal cells (AD-MSC and BMD-MSC) adhered to the scaffold surface and showed some proliferation: scaffold cell coverage was 25% after 72 h of incubation when seeded with 1000 cells/mm2 ; cells elongated processes along the polyamide-6, although they flattened 1.67-4 times less than on cell culture plastic. Human umbilical vein endothelial cells, however, showed poor adherence and proliferation. We thus provide in vitro evidence that polyamide-6 scaffolds approximating the esophageal biomechanics and 3D topography of nonhuman primates may provide a biocompatible substrate for both AD-MSC and BMD-MSCs, supporting their adhesion and survival to some degree. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 253-268, 2019.

Treatment of subcutaneous abscesses in children with incision and loop drainage: A simplified method of care.

PURPOSE: The aim of this study was to expand on our previous report of 115 patients after more than a decade-long experience using incision and loop drainage for pediatric subcutaneous abscess management. This report comprises the largest consecutive series of pediatric abscess patients from a single institution ever recorded. METHODS: A retrospective study was performed of all pediatric patients who underwent incision and loop drainage of subcutaneous abscesses at our institution between January 2002 and December 2014. TECHNIQUE: Two sub 5mm incisions were made at the periphery on the abscess. The abscess cavity was probed to break down loculations and drain pus. The abscess cavity was irrigated with normal saline. A loop drain was passed through one incision and brought out through the other. A simple absorbent dressing was applied over the drain. RESULTS: Five hundred seventy-six consecutive patients underwent loop drainage procedures. Mean values are as follows: age, 3.84years; duration of symptoms, 6.17days; postoperative length of stay (with 4 outliers excluded), 0.69days; drain duration, 8.38days; and number of postoperative visits, 1.28. Twenty-six patients had reoperations (4.5%), 2 of which were planned staged excisions of pilonidal cysts and 1 because of accidental home removal. CONCLUSIONS: Micro-incisions and loop drainage is a safe and effective treatment modality for subcutaneous abscesses in children. The findings eliminate the need for repetitive wound packing and simplify postoperative wound care. Loop drainage offers shorter time to discharge, lower recurrence rates, and minimal scarring. Additionally, there is expected cost reduction. We recommend this minimally invasive procedure to be the standard of care for subcutaneous abscesses in children. TYPE OF STUDY: Treatment study - retrospective review. LEVEL OF EVIDENCE: Level IV - case series with no comparison group.

Orthotopic transplantation of a tissue engineered diaphragm in rats.

The currently available surgical options to repair the diaphragm are associated with significant risks of defect recurrence, lack of growth potential and restored functionality. A tissue engineered diaphragm has the potential to improve surgical outcomes for patients with congenital or acquired disorders. Here we show that decellularized diaphragmatic tissue reseeded with bone marrow mesenchymal stromal cells (BM-MSCs) facilitates in situ regeneration of functional tissue. A novel bioreactor, using simultaneous perfusion and agitation, was used to rapidly decellularize rat diaphragms. The scaffolds retained architecture and mechanical properties and supported cell adhesion, proliferation and differentiation. Biocompatibility was further confirmed in vitro and in vivo. We replaced 80% of the left hemidiaphragm with reseeded diaphragmatic scaffolds. After three weeks, transplanted animals gained 32% weight, showed myography, spirometry parameters, and histological evaluations similar to native rats. In conclusion, our study suggested that reseeded decellularized diaphragmatic tissue appears to be a promising option for patients in need of diaphragmatic reconstruction.

Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy.

Granulocyte macrophage colony stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine. Its inflammatory activity is primarily due its role as a growth and differentiation factor for granulocyte and macrophage populations. In this capacity, among other clinical applications, it has been used to bolster anti-tumor immune responses. GM-CSF-mediated inflammation has also been implicated in certain types of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Thus, agents that can block GM-CSF or its receptor have been used as anti-inflammatory therapies. However, a review of literature reveals that in many situations GM-CSF can act as an anti-inflammatory/regulatory cytokine. We and others have shown that GM-CSF can modulate dendritic cell differentiation to render them "tolerogenic," which, in turn, can increase regulatory T-cell numbers and function. Therefore, the pro-inflammatory and regulatory effects of GM-CSF appear to depend on the dose and the presence of other relevant cytokines in the context of an immune response. A thorough understanding of the various immunomodulatory effects of GM-CSF will facilitate more appropriate use and thus further enhance its clinical utility.

Pediatric obesity.

Childhood obesity is a tremendous burden for children, their families, and society. Obesity prevention remains the ultimate goal but rapid development and deployment of effective nonsurgical treatment options is not currently achievable given the complexity of this disease. Surgical options for adolescent obesity have been proven to be safe and effective and should be offered. The development of stratified protocols of increasing intensity should be individualized for patients based on their disease severity and risk factors. These protocols should be offered in multidisciplinary, cooperative clinical trials to critically evaluate and develop optimal treatment strategies for morbid obesity.

Selective destruction of mouse islet beta cells by human T lymphocytes in a newly-established humanized type 1 diabetic model.

Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that leads to the loss of insulin-producing beta cells. The optimal preclinical testing of promising therapies would be aided by a humanized immune-mediated T1D model. We develop this model in NOD-scid IL2rgamma(null) mice. The selective destruction of pancreatic islet beta cells was mediated by human T lymphocytes after an initial trigger was supplied by the injection of irradiated spleen mononuclear cells (SMC) from diabetic nonobese diabetic (NOD) mice. This resulted in severe insulitis, a marked loss of total beta-cell mass, and other related phenotypes of T1D. The migration of human T cells to pancreatic islets was controlled by the beta cell-produced highly conserved chemokine stromal cell-derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor (CXCR) 4, as demonstrated by in vivo blocking experiments using antibody to CXCR4. The specificity of humanized T cell-mediated immune responses against islet beta cells was generated by the local inflammatory microenvironment in pancreatic islets including human CD4(+) T cell infiltration and clonal expansion, and the mouse islet beta-cell-derived CD1d-mediated human iNKT activation. The selective destruction of mouse islet beta cells by a human T cell-mediated immune response in this humanized T1D model can mimic those observed in T1D patients. This model can provide a valuable tool for translational research into T1D.

Dendritic cell-directed CTLA-4 engagement during pancreatic beta cell antigen presentation delays type 1 diabetes.

The levels of expression of alternatively spliced variants of CTLA-4 and insufficient CTLA-4 signaling have been implicated in type 1 diabetes. Hence, we hypothesized that increasing CTLA-4-specific ligand strength on autoantigen-presenting dendritic cells (DCs) can enhance ligation of CTLA-4 on T cells and lead to modulation of autoreactive T cell response. In this study, we show that DC-directed enhanced CTLA-4 engagement upon pancreatic beta cell Ag presentation results in the suppression of autoreactive T cell response in NOD mice. The T cells from prediabetic NOD mice treated with an agonistic anti-CTLA-4 Ab-coated DC (anti-CTLA-4-Ab DC) showed significantly less proliferative response and enhanced IL-10 and TGF-beta1 production upon exposure to beta cell Ags. Furthermore, these mice showed increased frequency of Foxp3+ and IL-10+ T cells, less severe insulitis, and a significant delay in the onset of hyperglycemia compared with mice treated with control Ab-coated DCs. Further analyses showed that diabetogenic T cell function was modulated primarily through the induction of Foxp3 and IL-10 expression upon Ag presentation by anti-CTLA-4-Ab DCs. The induction of Foxp3 and IL-10 expression appeared to be a consequence of increased TGF-beta1 production by T cells activated using anti-CTLA-4-Ab DCs, and this effect could be enhanced by the addition of exogenous IL-2 or TGF-beta1. Collectively, this study demonstrates the potential of a DC-directed CTLA-4 engagement approach not only in treating autoimmunity in type 1 diabetes, but also in altering diabetogenic T cell function ex vivo for therapy.

New type of human blood stem cell: a double-edged sword for the treatment of type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease caused by an autoimmune destruction of pancreatic islet insulin-producing cells. Autoimmunity and shortage of insulin-producing cells are 2 key issues for the treatment of T1D. To cure T1D in a comprehensive manner, both issues need to be addressed simultaneously. Not only must the islet cells be replaced, the patient's immune system also must be dealt with. Regulatory T cells (Tregs) play a crucial role in maintaining homeostasis and self-tolerance through their inhibitory impacts on autoreactive effector T cells. We identified a novel type of stem cells from human umbilical cord blood, designated cord blood stem cells (CB-SC), which may be able to address immune modulation of the autoimmune process and allow for beta-cell replacement. We are the first group using CB-SC to correct functional defects of CD4(+)CD62L(+) Tregs, leading to a reversal of overt diabetes in an autoimmune-caused diabetic NOD mouse model. Notably, treatment with CB-SC-modulated CD4(+)CD62L(+) Tregs (mCD4CD62L Tregs) simultaneously can overcome the autoimmunity via systemic and local immune modulations and the shortage of insulin-producing cells via stimulating the beta-cell regeneration. These new stem cells will offer a promising avenue for the development of powerful autologous therapeutic products for prevention and reversal of T1D.

A prospective trial for laparoscopic adjustable gastric banding in morbidly obese adolescents: an interim report of weight loss, metabolic and quality of life outcomes.

UNLABELLED: BACKGROUND AND MATERIALS AND METHODS: The outcome of patients completing 12 months of follow-up in a prospective longitudinal trial of the safety/efficacy of laparoscopic adjustable gastric banding (LAGB) for morbidly obese adolescents aged 14 to 17 years using a Food and Drug Administration Institutional Device Exemption for the use of the LAPBAND was analyzed. Baseline and outcome data were abstracted from a prospective database. RESULTS: Baseline (mean +/- SD) body mass index was 50 +/- 10 kg/m(2), and excess weight was 178 +/- 53 lb in 20 patients. Comorbidities included hypertension (45%), dyslipidemia (80%), insulin resistance (90%), metabolic syndrome (95%), and biopsy-proven nonalcoholic steatohepatitis (88%). At mean (SD) follow-up of 26 (9) months, % excess weight loss was 34% +/- 22% (n = 20) and 41% +/- 27% (n = 12), and the metabolic syndrome was resolved in 63% and 82% of the patients at 12 and 18 months, respectively. Hypertension normalized in all patients, along with improvement in lipid abnormalities and quality of life scores (P < .05). At 12 months, of the 5 patients with less than 20% excess weight loss, dyslipidemia and metabolic syndrome were resolved in 2 patients. CONCLUSION: At intermediate follow-up of a LAGB-based obesity treatment program, weight loss led to resolution or improvement of major obesity-related comorbidities in most patients, supporting the efficacy of LAGB as a surgical adjunct to a comprehensive obesity treatment program and its long-term evaluation.

Persistent hypoglycemia in a child with a gastrocolic fistula--an unexpected presentation of leucine-sensitive hypoglycemia.

Leucine-hypersensitive hypoglycemia is a rare clinical entity that is usually diagnosed after an exhaustive search for other causes of hypoglycemia. In nonsurgical patients, an imbalance between metabolic demands and gluconeogenesis are most frequently responsible for recurrent symptomatic hypoglycemia. In the postoperative patient, hypoglycemia more commonly results from inadequate energy intake or malabsorption from functional or anatomical abnormalities. Presented here is an unusual case of a child who was initially diagnosed with postoperative gastrocolic fistula and dumping syndrome as the cause of hypoglycemia but later found to have leucine-hypersensitive hypoglycemia.

Simultaneous costal cartilage-sparing modified Ravitch procedure and latissimus dorsi transfer for chest wall deformity repair in Poland's syndrome.

Poland's syndrome is a constellation of rare congenital anomalies that include hypoplasia of breast and underlying subcutaneous tissue, absence of the costosternal portion of the pectoralis major muscle, deformity or absence of ribs, absence of axillary hair, and syndactyly. Various surgical techniques have been described to repair such chest wall defects. We report a case of simultaneous Fonkalsrud procedure (costal cartilage-sparing version of the modified Ravitch procedure) and latissimus dorsi transfer in a 15-year-old boy with Poland's syndrome. The Fonkalsrud procedure has been used in the repair of pectus excavatum and pectus carinatum, and latissimus dorsi muscle transfer has been used in the repair of Poland's syndrome. In this report, we describe their combined use in an adolescent with severe pectus excavatum associated with Poland's syndrome. This combination of established operations resulted in a successful outcome.

Human cord blood stem cell-modulated regulatory T lymphocytes reverse the autoimmune-caused type 1 diabetes in nonobese diabetic (NOD) mice.

BACKGROUND: The deficit of pancreatic islet beta cells caused by autoimmune destruction is a crucial issue in type 1 diabetes (T1D). It is essential to fundamentally control the autoimmunity for treatment of T1D. Regulatory T cells (Tregs) play a pivotal role in maintaining self-tolerance through their inhibitory impact on autoreactive effector T cells. An abnormality of Tregs is associated with initiation of progression of T1D. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that treatment of established autoimmune-caused diabetes in NOD mice with purified autologous CD4(+)CD62L(+) Tregs co-cultured with human cord blood stem cells (CB-SC) can eliminate hyperglycemia, promote islet beta-cell regeneration to increase beta-cell mass and insulin production, and reconstitute islet architecture. Correspondingly, treatment with CB-SC-modulated CD4(+)CD62L(+) Tregs (mCD4CD62L Tregs) resulted in a marked reduction of insulitis, restored Th1/Th2 cytokine balance in blood, and induced apoptosis of infiltrated leukocytes in pancreatic islets. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that treatment with mCD4CD62L Tregs can reverse overt diabetes, providing a novel strategy for the treatment of type 1 diabetes as well as other autoimmune diseases.

Bilateral intrathoracic kidneys and adrenal glands associated with posterior congenital diaphragmatic hernias.

We present a case of bilateral intrathoracic kidneys and adrenal glands associated with bilateral posterior diaphragmatic defects in a symptomatic 18-month-old baby boy. The diaphragmatic defect did not appear to be the typical posterolateral diaphragmatic hernia of Bochdalek. The patient underwent primary surgical correction through an abdominal approach. Postoperatively, the patient enjoyed an uneventful course and was discharged home without any further events. We discuss this report of bilateral intrathoracic kidneys associated with bilateral diaphragmatic hernias, we describe the operative management, and we analyze the possible embryological development of this defect.

Preferential costimulation by CD80 results in IL-10-dependent TGF-beta1(+) -adaptive regulatory T cell generation.

Costimulatory ligands CD80 and CD86 have different binding preferences and affinities to their receptors, CD28 and CTLA-4. Earlier, we demonstrated that CD80 binds to CTLA-4 with higher affinity and has a role in suppressing T cell response. The current study demonstrates that not only did blockade of CD86 upon Ag presentation by bone marrow-derived dendritic cells (DC) to OVA-specific T cells result in induction of hyporesponsive T cells but also that these T cells could suppress the proliferative response of effector T cells. These T cells showed TGF-beta1 on their surface and secreted TGF-beta1 and IL-10 upon restimulation. Although blockade of CTLA-4 and neutralization of IL-10 profoundly inhibited the induction of these TGF-beta1(+) T cells, their ability to suppress the effector T cell proliferation was abrogated by neutralization of TGF-beta1 alone. Induction of TGF-beta1(+) and IL-10(+) T cells was found to be independent of natural CD4(+)CD25(+) regulatory T cells, demonstrating that preferential ligation of CTLA-4 by CD80 induced IL-10 production by effector T cells, which in turn promoted the secretion of TGF-beta1. Treatment of prediabetic NOD mice with islet beta cell Ag-pulsed CD86(-/-) DCs, but not CD80(-/-) DCs, resulted in the induction of TGF-beta1- and IL-10-producing cells, significant suppression of insulitis, and delay of the onset of hyperglycemia. These observations demonstrate not only that CD80 preferentially binds to CTLA-4 but also that interaction during Ag presentation can result in IL-10-dependent TGF-beta1(+) regulatory T cell induction, reinstating the potential of approaches to preferentially engage CTLA-4 through CD80 during self-Ag presentation in suppressing autoimmunity.

Enhanced engagement of CTLA-4 induces antigen-specific CD4+CD25+Foxp3+ and CD4+CD25- TGF-beta 1+ adaptive regulatory T cells.

CTLA-4 is a critical negative regulator of T cell response and is instrumental in maintaining immunological tolerance. In this article, we report that enhanced selective engagement of CTLA-4 on T cells by Ag-presenting dendritic cells resulted in the induction of Ag-specific CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)TGF-beta1(+) adaptive Tregs. These cells were CD62L(low) and hyporesponsive to stimulation with cognate Ag but demonstrated a superior ability to suppress Ag-specific effector T cell response compared with their CD62L(high) counterparts. Importantly, treatment of mice with autoimmune thyroiditis using mouse thyroglobulin (mTg)-pulsed anti-CTLA-4 agonistic Ab-coated DCs, which results in a dominant engagement of CTLA-4 upon self-Ag presentation, not only suppressed thyroiditis but also prevented reemergence of the disease upon rechallenge with mTg. Further, the disease suppression was associated with significantly reduced mTg-specific T cell and Ab responses. Collectively, our results showed an important role for selective CTLA-4 signaling in the induction of adaptive Tregs and suggested that approaches that allow dominant CTLA-4 engagement concomitant with Ag-specific TCR ligation can be used for targeted therapy.

Members of adenovirus species B utilize CD80 and CD86 as cellular attachment receptors.

Alternate serotypes of adenovirus (Ad), including Ads of species B, are being explored to circumvent the disadvantages of Ad serotype 5 gene delivery vectors. Whereas the majority of human Ads utilize the Coxsackievirus and adenovirus receptor (CAR), none of the Ad species B use CAR. Ad species B is further divided into two subspecies, B1 and B2, and utilizes at least two classes of receptors: common Ad species B receptors and B2 specific receptors. CD46 has been implicated as a B2-specific receptor. Ad serotype 3 (Ad3), a member of B1, utilizes CD80 and CD86 as cellular attachment receptors. The receptor-interacting Ad fiber-knob domain is highly homologous among species B Ads. We hypothesized that other members of Ad species B may utilize CD80 and CD86 as cellular attachment receptors. All tested species B members showed specific binding to cells expressing CD80 and CD86, and the Ad fiber-knob domain from both B1 and B2 Ad efficiently blocked CD80- and CD86-mediated infection of Ad3 vectors. Members of both B1 and B2 demonstrated CD80- and CD86-specific infection of CHO cells expressing CD80 and CD86. Therefore, all of the members of Ad species B utilize CD80 and CD86 for infection of cells.

Laparoscopic adjustable gastric banding for the treatment of adolescent morbid obesity in the United States: a safe alternative to gastric bypass.

BACKGROUND: Morbid obesity (MO) has reached epidemic proportions and is a major health problem in developed nations. In the adolescent with MO, early intervention can minimize obesity-related comorbidities, avoid premature mortality, improve quality of life, and prevent obesity-related diseases as these patients mature into adulthood. The primary surgical treatment of adolescent patients meeting National Institutes of Health criteria for bariatric surgery has been the gastric bypass (GB). Although GB has led to weight loss and improvement of comorbid conditions, concerns remain over the high incidence of postoperative complications and life-style-altering long-term sequelae of gastrointestinal tract reconstruction. Based on the excellent results from international adult series as well as the authors' own experience of more than 300 adult patients, laparoscopic adjustable gastric banding (LAGB) as an alternative to GB to eligible adolescents was offered. METHODS: After medical, psychologic, and nutritional screening, 4 patients (ages 17-19 years) with a body mass index of 40 or more (range, 40-61) who failed medical attempts at weight loss were selected for LAGB. RESULTS: The operative time was 40 to 90 minutes. All patients were discharged on the day of surgery. There were no early complications. One patient had cholecystitis 6 months after surgery requiring laparoscopic cholecystectomy. For the 4 patients, the amount of excess weight loss was 57% at 30 months, 34% at 12 months, 87% at 7 months, and 15% at 4 months, respectively. CONCLUSIONS: In this preliminary series of the US experience in the use of LAGB for the management of adolescents with MO, the lack of operative morbidity, short operative time/hospital stay, and encouraging initial weight loss mirror the adult experience and illustrate that the LAGB is a safe and effective alternative to GB. These encouraging results support further evaluation of LAGB as a surgical option in a comprehensive adolescent weight loss program.

Electron beam CT scan is a valuable and safe imaging tool for the pediatric surgical patient.

PURPOSE: Electron beam computed tomography (EBCT) is a relatively new technology that has been used primarily to detect coronary artery calcification in adult patients. EBCT has several potential advantages over traditional CT: (1) fast acquisition times resulting in less need for sedation, (2) decreased radiation exposure, and (3) robust software enabling real-time interactive 3-dimensional visualization of anatomic relationships. In this series of case reports, the authors describe their initial experience with the use of EBCT in pediatric noncardiac imaging. METHODS: Children with a variety of thoracic and abdominal disease processes were evaluated by EBCT. RESULTS: All patients underwent EBCT scanning without the need for sedation, and 3-dimensional images of the data sets were rendered in minutes after their acquisition. The diagnostic images provided equivalent spatial resolution to the multislice CT scanner but without motion artifacts and lower radiation exposure. CONCLUSIONS: EBCT is a safe, effective, and user- and patient-friendly alternative to traditional CT in the care of pediatric surgical diseases. The diagnostic yield of EBCT will continue to improve with new technologic advances and clinical experience.

Targeted CTLA-4 engagement induces CD4+CD25+CTLA-4high T regulatory cells with target (allo)antigen specificity.

CTLA-4 (CD152) is actively involved in down-regulating T cell activation and maintaining lymphocyte homeostasis. Our earlier studies showed that targeted engagement of CTLA-4 can down-modulate T cell response and suppress allo- and autoimmune responses. In this study, we report that targeted CTLA-4 engagement can induce immune tolerance to a specific target through selective induction of an Ag-specific CD4(+)CD25(+)CTLA-4(high) regulatory T cell (Treg cell) population. Allogeneic cells coated with anti-CTLA-4 Ab induced immune hyporesponsiveness through suppression of proinflammatory cytokines IFN-gamma and IL-2, and up-regulation of the regulatory cytokines IL-10, TGF-beta1, and IL-4, presumably through the engagement of CTLA-4 on activated T cells. Although rechallenge with alloantigen failed to break the unresponsiveness, a transient recovery from tolerance was observed in the presence of high concentrations of exogenous IL-2, saturating concentrations of neutralizing anti-TGF-beta1 and anti-IL-10 Abs, and blocking anti-CTLA-4 Ab, and upon depletion of CD4(+)CD25(+) Treg cells. The CD4(+)CD25(+)CTLA-4(high) Treg cells from tolerant mice suppressed the effector function of CD25(-) T cells from Ag-primed mice. Adoptive transfer of these Treg cells into Ag-primed mice resulted in a significantly reduced alloantigen-specific response. Further characterization demonstrated that the Treg cells with memory phenotype (CD62L(-)) were more potent in suppressing the alloantigen-specific T cell response. These results strongly support that the targeted engagement of CTLA-4 has therapeutic potential for the prevention of transplant rejection.

Adenovirus serotype 3 utilizes CD80 (B7.1) and CD86 (B7.2) as cellular attachment receptors.

Most viruses exploit a variety of host cellular proteins as primary cellular attachment receptors in the context of successful execution of infection. Furthermore, many viral agents have evolved precise mechanisms to subvert host immune recognition to achieve persistence. Herein we present data indicating that adenovirus (Ad) serotype 3 utilizes CD80 (B7.1) and CD86 (B7.2) as cellular attachment receptors. CD80 and CD86 are co-stimulatory molecules that are present on mature dendritic cells and B lymphocytes and are involved in stimulating T-lymphocyte activation. To our knowledge, this is one of the first demonstrations of a virus utilizing immunologic accessory molecules as a primary means of cellular entry. This finding suggests a mechanism whereby viral exploitation of these proteins as receptors may achieve both goals of cellular entry and evading the immune system.