Relationships of pulmonary function, inflammation, and T-cell activation and senescence in an HIV-infected cohort.

Objective: To determine associations between circulating markers of immune activation, immune cell senescence, and inflammation with HIV-associated abnormalities of pulmonary function.

Design: HIV infection is an independent risk factor for abnormal pulmonary function. Immune activation, immune senescence, and chronic inflammation are characteristics of chronic HIV infection that have been associated with other HIV-associated comorbidities and may be related to pulmonary disease in this population.

Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme.

The renal endothelium has been debated as arising from resident hemangioblast precursors that transdifferentiate from the nephrogenic mesenchyme (vasculogenesis) and/or from invading vessels (angiogenesis). While the Foxd1-positive renal cortical stroma has been shown to differentiate into cells that support the vasculature in the kidney (including vascular smooth muscle and pericytes) it has not been considered as a source of endothelial cell progenitors. In addition, it is unclear if Foxd1-positive mesenchymal cells in other organs such as the lung have the potential to form endothelium.

Patients with cystic fibrosis have inducible IL-17+IL-22+ memory cells in lung draining lymph nodes.

Background: IL-17 is an important cytokine signature of the TH differentiation pathway TH17. This T-cell subset is crucial in mediating autoimmune disease or antimicrobial immunity in animal models, but its presence and role in human disease remain to be completely characterized.

Objective: We set out to determine the frequency of TH17 cells in patients with cystic fibrosis (CF), a disease in which there is recurrent infection with known pathogens.

Integration of immunity with physical and cognitive function in definitions of successful aging.

Studies comparing chronologically "young" versus "old" humans document age-related decline of classical immunological functions. However, older adults aged ≥65 years have very heterogeneous health phenotypes. A significant number of them are functionally independent and are surviving well into their 8(th)-11(th) decade life, observations indicating that aging or old age is not synonymous with immune incompetence.

Isolation and characterization of human anterior cruciate ligament-derived vascular stem cells.

The anterior cruciate ligament (ACL) usually fails to heal after rupture mainly due to the inability of the cells within the ACL tissue to establish an adequate healing process, making graft reconstruction surgery a necessity. However, some reports have shown that there is a healing potential of ACL with primary suture repair. Although some reports showed the existence of mesenchymal stem cell-like cells in human ACL tissues, their origin still remains unclear.

Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is caused by a dominant Th2 immune response to antigens derived from the opportunistic mold Aspergillus, most commonly Aspergillus fumigatus. It occurs in 4%-15% of patients with cystic fibrosis (CF); however, not all patients with CF infected with A. fumigatus develop ABPA.

Interleukin-17 is required for T helper 1 cell immunity and host resistance to the intracellular pathogen Francisella tularensis.

The importance of T helper type 1 (Th1) cell immunity in host resistance to the intracellular bacterium Francisella tularensis is well established. However, the relative roles of interleukin (IL)-12-Th1 and IL-23-Th17 cell responses in immunity to F. tularensis have not been studied.

Human embryonic stem cell-derived hematoendothelial progenitors engraft chicken embryos.

Objective: To investigate whether human embryonic stem cells (hESC) committed in culture into hematopoietic/endothelial cell progenitors can be further developed into mature blood and vascular cells following transplantation into chicken embryos.

Materials And Methods: The yolk sac of 42- to 44-hour chicken embryos received yolk sac injections of unfractionated human embryoid body (hEB) cells, CD34-positive hEB cells, or CD34+CD45+ granulocyte colony-stimulating factor-mobilized human peripheral blood hematopoietic stem-progenitor cells. Human cells in the host were detected by flow cytometry and immunohistochemistry.

Purification and culture of human blood vessel-associated progenitor cells.

Multilineage progenitor cells, diversely designated as MSC, MAPC, or MDSC, have been previously extracted from long-term cultures of fetal and adult organs (e.g., bone marrow, brain, lung, pancreas, muscle, adipose tissue, and several others).

TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice.

Steroid-resistant asthma comprises an important source of morbidity in patient populations. T(H)17 cells represent a distinct population of CD4(+) Th cells that mediate neutrophilic inflammation and are characterized by the production of IL-17, IL-22, and IL-6. To investigate the function of T(H)17 cells in the context of Ag-induced airway inflammation, we polarized naive CD4(+) T cells from DO11.

A reservoir of brown adipocyte progenitors in human skeletal muscle.

Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration.

Optimizing CO2 normalizes pH and enhances chondrocyte viability during cold storage.

Fresh osteochondral allografts are an important treatment option for the repair of full-thickness articular cartilage defects. Viable chondrocytes within the transplanted tissue are considered important to maintaining matrix integrity. The purpose of this study is to determine whether an increase in pH decreases chondrocyte viability during cold storage and whether equilibration of Dulbecco's modified Eagle's medium (DMEM) in 5% CO(2) normalizes pH and increases chondrocyte survival during storage at 4 degrees C.

Prospective identification of myogenic endothelial cells in human skeletal muscle.

We document anatomic, molecular and developmental relationships between endothelial and myogenic cells within human skeletal muscle. Cells coexpressing myogenic and endothelial cell markers (CD56, CD34, CD144) were identified by immunohistochemistry and flow cytometry. These myoendothelial cells regenerate myofibers in the injured skeletal muscle of severe combined immunodeficiency mice more effectively than CD56+ myogenic progenitors.

Regulatory T cells dampen pulmonary inflammation and lung injury in an animal model of pneumocystis pneumonia.

CD4+CD25+FoxP3+ regulatory T cells are decreased in patients infected with HIV and have been shown to be critical in mediating Ag tolerance in the lung. Because a subset of Pneumocystis-infected individuals develop substantial lung injury, which can be modeled in immune reconstituted scid mice, we used mouse models of Pneumocystis carinii to investigate the role of regulatory T cells in opportunistic infection and immune reconstitution. In this study, we show that CD4+CD25+FoxP3+ cells are part of the host response to Pneumocystis in CD4+ T cell-intact mice.

Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells.

Exosomes are nanovesicles released by leukocytes and epithelial cells. Although their function remains enigmatic, exosomes are a source of antigen and transfer functional major histocompatibility complex (MHC)-I/peptide complexes to dendritic cells (DCs) for CD8(+) T-cell activation. Here we demonstrate that exosomes also are internalized and processed by immature DCs for presentation to CD4(+) T cells.

Porcine cell microchimerism but lack of productive porcine endogenous retrovirus (PERV) infection in naive and humanized SCID-beige mice treated with porcine peripheral blood mononuclear cells.

Pigs are considered a suitable source of cells and organs for xenotransplantation. All known strains of pigs contain porcine endogenous retrovirus (PERV) and PERV released by porcine cells may infect human cells in vitro and severe-combined immunodeficient (SCID) mice in vivo. Humanized SCID (hu-SCID) mice develop immune response to porcine antigens.

Comparative evaluation of CC chemokine-induced migration of murine CD8alpha+ and CD8alpha- dendritic cells and their in vivo trafficking.

Murine CD11c(+)CD8alpha(-) and CD11c(+)CD8alpha(+) dendritic cells (DCs) differentially regulate T cell responses. Although specific chemokines that recruit immature (i) or mature (m) CD8alpha(-) DCs have been identified, little is known about the influence of chemokines on CD8alpha(+) DCs. iDCs and mDCs isolated from spleens of fms-like tyrosine kinase 3 ligand-treated B10 mice were compared directly for migratory responses to a panel of CC chemokines or following local or systemic administration.

Type-1 polarized nature of mouse liver CD8alpha- and CD8alpha+ dendritic cells: tissue-dependent differences offset CD8alpha-related dendritic cell heterogeneity.

Interleukin-12 p70 (IL-12p70) is a major dendritic cell (DC)-produced cytokine known to support type-1 T helper (Th1) cells and inflammatory-type immunity. While the ability of DC to produce bioactive IL-12p70 depends on both the DC subtype and the microenvironmental conditions of DC development, the relative contribution of each of these factors remains unclear. Here, we report that in contrast to spleen CD8alpha+ and CD8alpha- DC that show strong differences in their respective IL-12p70-producing capacities, CD8alpha+ and CD8alpha- DC isolated from the liver, a non-lymphoid organ, both efficiently produce IL-12p70 in amounts comparable to spleen CD8alpha+ DC.

Four-color flow cytometric analysis of peripheral blood donor cell chimerism.

Passenger leukocytes have been demonstrated to play significant roles in initiating and also regulating immune reactions after organ transplantation. Reliable techniques to detect donor leukocytes in recipients after organ transplantation are essential to analyze the role, function, and behavior of these leukocytes. In this report we describe a simple, reliable method to detect donor cells with low frequencies using peripheral blood samples.

Dendritic cell subsets in blood and lymphoid tissue of rhesus monkeys and their mobilization with Flt3 ligand.

We provide phenotypic and functional evidence of premonocytoid dendritic cells (DCs) and preplasmacytoid DCs in blood and of corresponding DC subsets in secondary lymphoid tissue of rhesus monkeys. Subsets were identified and sorted by 4-color flow cytometry using antihuman monoclonal antibodies cross-reactive with rhesus monkey. To mobilize pre-DC subsets, fms-like tyrosine 3 kinase ligand (Flt3L; 100 microg/kg subcutaneously) was administered for 10 days.

Rapamycin inhibits IL-4--induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo.

Rapamycin (RAPA) is a potent immunosuppressive macrolide hitherto believed to mediate its action primarily via suppression of lymphocyte responses to interleukin 2 (IL-2) and other growth factors. We show here that this view is incomplete and provide evidence that RAPA suppresses the functional activation of dendritic cells (DCs) both in vitro and in vivo. In vitro, RAPA inhibits IL-4-dependent maturation and T-cell stimulatory activity of murine bone marrow-derived DCs.

Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production.

Under steady-state conditions, internalization of self-antigens embodied in apoptotic cells by dendritic cells (DCs) resident in peripheral tissue followed by DC migration and presentation of self-peptides to T cells in secondary lymphoid organs are key steps for induction and maintenance of peripheral T-cell tolerance. We show here that, besides this traffic of apoptotic cells mediated by peripheral tissue-resident DCs, splenic marginal zone DCs rapidly ingest circulating apoptotic leukocytes, process apoptotic cell-derived peptides into major histocompatibility complex class II (MHC-II) molecules, and acquire CD8alpha during their mobilization to T-cell areas of splenic follicles. Because apoptotic cells activate complement and some complement factors are opsonins for phagocytosis and play roles in the maintenance of peripheral tolerance, we investigated the role of complement receptors (CRs) in relation to phagocytosis of apoptotic cells by DCs.

Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells.

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that use 2 major pathways for antigen uptake: constitutive macropinocytosis and mannose receptor-mediated endocytosis. Efficient endocytosis is critical for DCs to fulfill their sentinel function in immunity. We investigated the influence of the immunosuppressive macrolide rapamycin on macropinocytosis of fluorescein isothiocyanate (FITC)-albumin and mannose receptor-mediated endocytosis of FITC-dextran by murine bone marrow-derived DCs by flow cytometry.

Use of recombinase activation gene-2 deficient mice to ascertain the role of cellular and humoral immune responses in the development of chronic rejection.

Introduction: Given its multifactorial etiology, the relative contribution of anti-donor cellular and humoral immune responses in the pathogenesis of chronic rejection is as yet ambiguous. We hypothesized that alloreactive T and B cells play a seminal role in the development of this lesion.

Methods: To address this hypothesis, RAG-2(-/-) mice were used as donors and recipients in a well-established murine model of aortic transplantation.