Significance We show that tumor reprogramming of hematopoiesis in bone marrow occurs at the onset malignant conversion and results systemic expansion circulating activated neutrophils preferentially accumulate lungs. Our data are, to our knowledge, first activation not inhibition myeloid differentiation is responsible for activity T cell-suppressive cells; a tumor-derived factor targets immature hematopoietic compartment drive expansion; granulocyte-colony stimulating (G-CSF) only growth...

The mechanism by which the immune system produces effector and memory T cells is largely unclear. To allow a large-scale assessment of development single naive into different subsets, we have developed technology that introduces unique genetic tags (barcodes) cells. By comparing barcodes present in antigen-specific cell populations systemic local infection models, at anatomical sites, for TCR-pMHC interactions avidities, demonstrate under all conditions tested, individual yield both CD8+...

The magnitude of antigen-specific CD8+ T cell responses is not fixed but correlates with the severity infection. Although by definition response size product both capacity to recruit naïve cells (clonal selection) and their subsequent proliferation expansion), it remains undefined how these two factors regulate responses. We determined relative contribution recruitment expansion labeling unique genetic tags transferring them into mice. Under disparate infection conditions different pathogens...

Significance Previous work showed that primary tumors instigate systemic macroenvironmental changes supporting cancer progression and metastasis. Here, we show activation of HIF signaling in osteoblast-lineage cells also generates promoting breast growth dissemination bones outside the skeleton. Our results indicate loss bone homeostasis through alterations anabolism could affect present skeleton as an important organ tumor macroenvironment. They suggest targeting microenvironment limit cancer.

In vivo priming of antigen-specific CD8+ T cells results in their expansion and differentiation into effector followed by contraction a memory cell population that can be maintained for life. Recent evidence suggests after initial antigenic stimulation, the magnitude kinetics response are programmed. However, it is unclear to what extent instruction modulated costimulatory signals. Here, we demonstrate constitutive ligation tumor necrosis factor receptor family member CD27 its ligand CD70...

T cells, as well other cell types, are composed of phenotypically and functionally distinct subsets. However, for many these populations it is unclear whether they develop from common or separate progenitors. To address such issues, we developed a novel approach, termed cellular barcoding, that allows the dissection lineage relationships. We demonstrate labeling cells with unique identifiers coupled to microarray-based detection system can be used analyze family relationships between progeny...

Abstract Autophagy is a highly regulated catabolic process that involves sequestration and lysosomal degradation of cytosolic components such as damaged organelles misfolded proteins. While autophagy can be considered to general cellular housekeeping process, it has become clear may also play cell type-dependent functional roles. In this study, we analyzed the importance in human hematopoietic stem/progenitor cells (HSPCs), how during differentiation. Western blot-based analysis LC3-II p62...

Despite the accepted role for CD4+ T cells in immune control, little is known about development of Ag-specific cell immunity upon primary infection. Here we use MHC class II tetramer technology to directly visualize response infection mice with Moloney murine sarcoma and leukemia virus complex (MoMSV). Significant numbers are detected both lymphoid organs retrovirus-induced lesions early during infection, they express 1B11-reactive activation-induced isoform CD43 that was recently shown...

Abstract Cartilage has little intrinsic capacity for repair, so transplantation of exogenous cartilage cells is considered a realistic option regeneration. We explored whether human-induced pluripotent stem (hiPSCs) could represent such unlimited cell sources neo-cartilage comparable to human primary articular chondrocytes (hPACs) or bone marrow-derived mesenchymal stromal (hBMSCs). For this, chondroprogenitor (hiCPCs) and hiPSC-derived (hiMSCs) were generated from two independent hiPSC...

Cell-based therapies have the potential to become treatment options for many diseases, but efficient scale-out of these has proven be a major hurdle. Bioreactors can used overcome this hurdle, changing culture method introduce unwanted changes cell product. Therefore, it is important establish parity between products generated using traditional methods versus those bioreactor. Mesenchymal stromal cells (MSCs) are cultured in parallel either flasks, spinner vessels or new bioreactor system....

To introduce a functional vascular network into tissue-engineered bone equivalents, human endothelial colony forming cells (ECFCs) and multipotent mesenchymal stromal (MSCs) can be cocultured. Here, we studied the impact of donor variation marrow-derived MSCs cord blood-derived ECFCs on vasculogenesis osteogenesis using 3D in vitro coculture model. Further, to make step towards cocultures consisting derived from single donor, tested how induced pluripotent stem cell (iPSC)-derived (iECs)...

Abstract CD4+ T cells that are activated by a MHC class II/peptide encounter can induce maturation of APCs and promote cytotoxic CD8+ cell responses. Unfortunately, the number well-defined tumor-specific epitopes be exploited for adoptive immunotherapy is limited. To determine whether Th responses generated redirecting to I ligands, we have introduced I-restricted TCRs into postthymic murine examined activation helper function in vitro vivo. These experiments indicate Ag-specific help...

ABSTRACT Therapeutic strategies for the treatment of acute retroviral infections have relied mainly on antiviral drugs. In this study we used Friend virus model system to demonstrate that enhancement immune can also dramatic therapeutic effects. Since resistance virus-induced leukemia in mice is associated with T helper cell type 1 (Th1) responses, enhanced these responses susceptible by synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN). Treatments begun at 4 days...

Secondary T cell responses are enhanced because of an expansion in numbers antigen-specific (memory) cells. Using major histocompatibility complex class II tetramers we have tracked peptide-specific endogenous (non–T receptor transgenic) CD4 memory cells normal and costimulation-deficient mice. were detectable after immunization for more than 200 days, although decay was apparent. Memory generated CD40 knockout mice by with peptide-pulsed wild-type dendritic survived the absence proliferated...

Reconstruction of the bladder by means both natural and synthetic materials remains a challenge due to severe adverse effects such as mechanical failure. Here we investigate application spider major ampullate gland-derived dragline silk from Nephila edulis spider, biomaterial with outstanding properties slow degradation rate, potential scaffold for reconstruction studying cellular response primary cells this biomaterial. We demonstrate that without any additional biological coating supports...

The current studies demonstrate complex and seemingly contradictory effects by gamma interferon (IFN-gamma) on Friend virus (FV) infection. Both temporal tissue-specific were observed. During the first week of infection, IFN-gamma-deficiency caused increased levels FV infection in multiple tissues. Surprisingly, however, 2 weeks postinfection, IFN-gamma-deficient mice had significantly lower both spleen bone marrow compared to wild-type mice. rapid reduction correlated with a more...

The bone marrow (BM) niche is essential for lifelong hematopoietic stem cell (HSC) maintenance, proliferation and differentiation. Several BM types, including osteoblast lineage cells (OBC), mesenchymal (MSC) endothelial (EC) have been implicated in supporting HSC location function, but the relative importance of these types their secreted ligands remain controversial. We recently found that surface receptors Robo4 CXCR4 cooperate to localize niches. hypothesized Slit2, a putative ligand...