Human red blood cells have an enhancing effect on the relative expansion of CD8+ T lymphocytes in vitro

Cell Prolif. 2001 Dec;34(6):359-67. Human red blood cells have an enhancing effect on the relative expansion of CD8+ T lymphocytes in vitro. Porto B, Fonseca AM, Godinho I, Arosa FA, Porto G. Laboratory of Cytogenetics, Abel Salazar Institute for the Biomedical Sciences (ICBAS), Porto, Portugal. [email protected] Abstract The present study was designed to analyse the effect of red blood cells on T-cell proliferation and expansion. A comparative study was done in peripheral blood cell cultures stimulated with phytohemagglutinin, with or without red blood cells. The presence of red blood cells had a consistent enhancing effect on T lymphocyte proliferation, as determined by an increase in both the mitotic index and thymidine uptake. Phenotypic characterization of T cell blasts by flow cytometry revealed that, in the presence of red blood cells, expanding cells were preferentially CD8+ cells. Accordingly, proliferation of CD8+ lymphocytes from two patients with CD8+ hyperlymphocytosis was dependent on the presence of red blood cells. In contrast, proliferation of CD4+ lymphocytes from two patients with CD4+ hyperlymphocytosis was strongly inhibited by the presence of red blood cells. This is the first reported evidence that human red blood cells have an enhancing effect on the expansion of CD8+ lymphocytes in vitro. PMID: 11737000 [PubMed - indexed for MEDLINE

Boards of directors in SMEs: An empirical evidence of board task performance

This paper seeks to provide a better understanding of what makes boards effective. We analyse the relationships between board demography and company performance and between working structures and board tasks in small and medium-sized enterprises (SMEs). We test our hypotheses on a sample of 307 Spanish SMEs. The main empirical result is the negative impact that the proportion of outside directors and the board size have on firm performance. We also find a negative impact of outsiders’ presence and a positive impact of director tenure on the board’s service role. Our analysis of the role of board control highlights the negative relationship between this variable and CEO tenure

Spatial Division Multiplexing for Multiplex Coherent Anti-Stokes Raman Scattering

We demonstrate how a narrowband pump and a broadband spectrum can be spatially multiplexed by selective coupling them in two distinct modes of a few-mode microstructure fiber. The first mode carries most of the input pump energy, and experiences spectral broadening. Whereas the second mode preserves the narrow bandwidth of the remaining part of the pump. Bimodal propagation, with a power unbalance strongly in favor of the fundamental mode, is naturally obtained by maximizing coupling into the fundamental mode of the fiber. At the fiber output, the nearly monochromatic beam and the supercontinuum carried by the two different modes are combined by a microscope objective, and used as a pump and a Stokes wave for self-referenced multiplex coherent anti-Stokes Raman scattering micro-spectroscopy. The spectral resolution, the signal-to-noise-ratio, and the possible amplification of the remaining pump beam are discussed.Comment: 10 pages, 9 figure

A Potential Role for Shed Soluble Major Histocompatibility Class I Molecules as Modulators of Neurite Outgrowth

The neurobiological activities of classical major histocompatibility class I (MHCI) molecules are just beginning to be explored. To further examine MHCI's actions during the formation of neuronal connections, we cultured embryonic mouse retina explants a short distance from wildtype thalamic explants, or thalami from transgenic mice (termed “NSE-Db”) whose neurons express higher levels of MHCI. While retina neurites extended to form connections with wildtype thalami, we were surprised to find that retina neurite outgrowth was very stunted in regions proximal to NSE-Db thalamic explants, suggesting that a diffusible factor from these thalami inhibited retina neurite outgrowth. It has been long known that MHCI-expressing cells release soluble forms of MHCI (sMHCI) due to the shedding of intact MHCI molecules, as well as the alternative exon splicing of its heavy chain or the action proteases which cleave off it's transmembrane anchor. We show that the diffusible inhibitory factor from the NSE-Db thalami is sMHCI. We also show that COS cells programmed to express murine MHCI release sMHCI that inhibits neurite outgrowth from nearby neurons in vitro. The neuroinhibitory effect of sMHCI could be blocked by lowering cAMP levels, suggesting that the neuronal MHCI receptor's signaling mechanism involves a cyclic nucleotide-dependent pathway. Our results suggest that MHCI may not only have neurobiological activity in its membrane-bound form, it may also influence local neurons as a soluble molecule. We discuss the involvement of complement proteins in generating sMHCI and new theoretical models of MHCI's biological activities in the nervous system

HLA-C and HIV-1: friends or foes?

The major histocompatibility complex class I protein HLA-C plays a crucial role as a molecule capable of sending inhibitory signals to both natural killer (NK) cells and cytotoxic T lymphocytes (CTL) via binding to killer cell Ig-like receptors (KIR). Recently HLA-C has been recognized as a key molecule in the immune control of HIV-1. Expression of HLA-C is modulated by a microRNA binding site. HLA-C alleles that bear substitutions in the microRNA binding site are more expressed at the cell surface and associated with the control of HIV-1 viral load, suggesting a role of HLA-C in the presentation of antigenic peptides to CTLs. This review highlights the role of HLA-C in association with HIV-1 viral load, but also addresses the contradiction of the association between high cell surface expression of an inhibitory molecule and strong cell-mediated immunity. To explore additional mechanisms of control of HIV-1 replication by HLA-C, we address specific features of the molecule, like its tendency to be expressed as open conformer upon cell activation, which endows it with a unique capacity to associate with other cell surface molecules as well as with HIV-1 proteins

Defining family business: a closer look at definitional heterogeneity

Researchers have used a myriad of different definitions in seeking to explain the heterogeneity of family firms and their unique behavior; however, no widely-accepted definition exists today. Definitional clarity in any field is essential to provide (a) the basis for the analysis of performance both spatially and temporally and (b) the foundation upon which theories, frameworks and models are developed. We provide a comprehensive analysis of prior research and identify and classify 82 definitions of family business. We then review and evaluate five key theoretical perspectives in family business to identify how these have shaped and informed the definitions employed in the field and duly explain family firm heterogeneity. Finally, we provide a conceptual diagram to inform the choice of definition in different research settings

Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28− T cells

The present study consists of a phenotypic and functional characterization of peripheral blood T lymphocytes in a group of 21 patients with hereditary haemochromatosis (HH), an MHC class I-linked genetic disease resulting in iron overload, and a group of 30 healthy individuals, both HLA-phenotyped. The HH patients studied showed an increased percentage of CD8+ CD28− T cells with a corresponding reduction in the percentage of CD8+ CD28+ T cells in peripheral blood relative to healthy blood donors. No anomalies of CD28 expression were found in the CD4+ subset. The presence of the HLA-A3 antigen but not age accounted for these imbalances. Thus, an apparent failure of the CD8+ CD28+ T cell population ‘to expand’, coinciding with an ‘expansion’ of CD8+ CD28− T cells in peripheral blood of HLA-A3+ but not HLA-A3− HH patients was observed when compared with the respective HLA-A3-matched control group. A significantly higher percentage of HLA-DR+ but not CD45RO+ cells was also found within the peripheral CD8+ T cell subset in HH patients relative to controls. Phytohaemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMC) for 5 days showed: (i) that CD8+ CD28+ T cells both in controls and HH were able to expand in vitro; (ii) that CD8+ CD28− T cells decreased markedly after activation in controls but not in HH patients. Moreover, functional studies showed that CD8+ cytotoxic T lymphocytes (CTL) from HH patients exhibited a diminished cytotoxic activity (approx. two-fold) in standard 51Cr-release assays when compared with CD8+ CTL from healthy controls. The present results provide additional evidence for the existence of phenotypic and functional anomalies of the peripheral CD8+ T cell pool that may underlie the clinical heterogeneity of this iron overload disease. They are of particular relevance given the recent discovery of a novel mutated MHC class I-like gene in HH

Spatial Division Multiplexing for Multiplex Coherent Anti-Stokes Raman Scattering

International audienceWe demonstrate how a narrowband pump and a broadband spectrum can be spatially multiplexed by selective coupling them in two distinct modes of a few-mode microstructure fiber. The first mode carries most of the input pump energy, and experiences spectral broadening. Whereas the second mode preserves the narrow bandwidth of the remaining part of the pump. Bimodal propagation, with a power unbalance strongly in favor of the fundamental mode, is naturally obtained by maximizing coupling into the fundamental mode of the fiber. At the fiber output, the nearly monochromatic beam and the supercontinuum carried by the two different modes are combined by a microscope objective, and used as a pump and a Stokes wave for self-referenced multiplex coherent anti-Stokes Raman scattering micro-spectroscopy. The spectral resolution, the signal-to-noise-ratio, and the possible amplification of the remaining pump beam are discussed