The size and phenotype of virus-specific T cell populations is determined by repetitive antigenic stimulation and environmental cytokines.

Based on the expression of the TNFR SFP CD27, two Ag-primed CD8(+) T cell subsets can be discerned in the circulation of healthy individuals: CD27(+) T cells that produce a variety of cytokines but do not display immediate cytolytic activity; and cytotoxic CD27(-) T cells, which secrete only IFN-gamma and TNF-alpha. The mechanism that controls the generation of these different phenotypes is unknown. We show that CMV reactivation not only increases the number of virus-specific T cells but also induces their transition from a CD27(+) to a CD27(-) phenotype.

B cells are crucial for both development and maintenance of the splenic marginal zone.

The splenic marginal zone is a unique compartment that separates the lymphoid white pulp from the surrounding red pulp. Due to the orchestration of specialized macrophages and B cells flanking a marginal sinus, this compartment plays an important role in uptake of blood-borne Ags and it gives the spleen its specialized function in antibacterial immunity. In this study, we demonstrate that both development and maintenance of this marginal zone is highly dependent on the presence of B cells.

Effects of CD25 monoclonal antibody on proliferative and effector functions of alloactivated human T cells in vitro.

Prophylactic treatment with CD25 mAb has led to a significant decrease of acute rejection rates after renal transplantation. However, despite its inhibitory effect on T cell proliferation and effector functions, rejections still occur. To obtain more insight in persistent alloreactivity, we evaluated the effects of the chimeric IgG1kappa CD25 mAb Basiliximab on proliferation and differentiation of alloactivated T cells from healthy individuals in vitro.

The epidermal growth factor-seven transmembrane (EGF-TM7) receptor CD97 is required for neutrophil migration and host defense.

The epidermal growth factor-seven transmembrane (EGF-TM7) family is a group of seven-span transmembrane receptors predominantly expressed by cells of the immune system. Family members CD97, EGF module-containing mucin-like receptor (EMR) 1, EMR2, EMR3, EMR4, and EGF-TM7-latrophilin-related protein are characterized by an extended extracellular region with a variable number of N-terminal EGF-like domains. EGF-TM7 receptors bind cellular ligands as demonstrated by the interaction of CD97 with decay accelerating factor (CD55) and dermatan sulfate.

Object-based connectedness facilitates matching.

In two matching tasks, participants had to match two images of object pairs. Image-based (IB) connectedness refers to connectedness between the objects in an image. Object-based (OB) connectedness refers to connectedness between the interpreted objects.

Spontaneous outgrowth of EBV-transformed B-cells reflects EBV-specific immunity in vivo; a useful tool in the follow-up of EBV-driven immunoproliferative disorders in allograft recipients.

During immunosuppressive medication, Epstein-Barr virus (EBV) infection is associated with a risk of developing posttransplant lymphoproliferative disease (PTLD). The appropriateness of a spontaneous EBV B-cell transformation (SET) assay as a monitor of EBV-specific immunity was evaluated to investigate if it safely allows reducing immunosuppressive medication, thereby decreasing the risk of developing PTLD. PBMC were isolated longitudinally from 20 pediatric renal allograft recipients treated with prednisone and cyclosporine combined with either azathioprine or mycophenolate mofetil.

Cytokine producing CD8+ T cells are correlated to MRI features of tissue destruction in MS.

Specific T-cell subsets and their ability to produce cytokines have been involved in concepts of multiple sclerosis (MS) pathogenesis. Evidence to link cytokine producing T-cell subsets to magnetic resonance imaging (MRI) features of tissue destruction, however, is limited. Cytokine flow cytometry was performed in 124 patients with different subtypes of MS.

Differential effects of object orientation on imaginary object/viewer transformations.

Given a specific view of a simple symmetrical object, participants were asked whether a certain imaginary transformation could result in a second viewed image. An experiment was conducted in which the participants had either to mentally rotate an object or to imagine themselves looking at the object from another position (i.e.

IL-15 induces antigen-independent expansion and differentiation of human naive CD8+ T cells in vitro.

Recent studies in mice have shown that although interleukin 15 (IL-15) plays an important role in regulating homeostasis of memory CD8+ T cells, it has no apparent function in controlling homeostatic proliferation of naive T cells. We here assessed the influence of IL-15 on antigen-independent expansion and differentiation of human CD8+ T cells. Both naive and primed human T cells divided in response to IL-15.

Type I IFNs differentially modulate IL-12p70 production by human dendritic cells depending on the maturation status of the cells and counteract IFN-gamma-mediated signaling.

Type I IFNs (IFNalpha/beta) are approved for the treatment of a variety of diseases, including the autoimmune disease multiple sclerosis (MS). The proinflammatory cytokines IL-12 and IFN-gamma have been proposed to contribute to the pathogenesis of MS. Since dendritic cells (DCs) are recognized as major producers of IL-12p70 and promote the development of IFN-gamma-producing Th1 cells, we investigated the direct effect of IFNalpha/beta on monocyte-derived DCs at different stages of development.

Inactivation of the EGF-TM7 receptor EMR4 after the Pan-Homo divergence.

We here report on the identification of a novel human EGF-TM7 receptor, designated EMR4. Like most EGF-TM7 receptor genes, EMR4 is localized on the short arm of chromosome 19, in close proximity to EMR1. Remarkably, due to a one-nucleotide deletion in exon 8, translation of human EMR4 would result in a truncated 232-amino acid protein lacking the entire seven-span transmembrane region.

Intra- and interocular colour-specific activation during dichoptic suppression.

A new psychophysical method, based on dichoptic suppression, is introduced to study intra- and interocular colour activations. An experiment is performed which shows that activation of a specific colour in one eye may cancel suppression of the same colour in the ipsi-lateral eye or in the contra-lateral eye at non-corresponding retinal locations. A control experiment shows that the effect is not due to an overall response-bias to the activated colour.

Frequencies of circulating cytolytic, CD45RA+CD27-, CD8+ T lymphocytes depend on infection with CMV.

Viral infections may cause serious disease unless the adaptive immune system is able to clear the viral agents through its effector arms. Recent identification and functional characterization of subpopulations of human CD8(+) T cells has set the stage to study the correlation between the appearance of particular subsets and common viral infections during childhood, i.e.

Expansion of CMV-specific CD8+CD45RA+CD27- T cells in B-cell chronic lymphocytic leukemia.

In patients with B-cell chronic lymphocytic leukemia (B-CLL), the absolute number of T cells is increased. Although it has been suggested that these T cells might be tumor specific, concrete evidence for this hypothesis is lacking. We performed a detailed immunophenotypic analysis of the T-cell compartment in the peripheral blood of 28 patients with B-CLL (Rai 0, n = 12; Rai I-II, n = 10; Rai III-IV, n = 6) and 12 healthy age-matched controls and measured the ability of these patients to mount specific immune responses.

Expression of the murine CD27 ligand CD70 in vitro and in vivo.

The interaction between TNFR family member CD27 and its ligand CD70 promotes lymphocyte expansion and effector cell formation. In humans, control of CD27 function is partly regulated by the restricted expression of CD70. We used newly developed mAbs to characterize murine (m) CD70 expression in vitro and in vivo.

Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions.

It has been proposed that HIV-1, in addition to directly infecting and killing CD4+ T cells, causes T cell dysfunction and T cell loss by chronic immune activation. We analyzed the effects of chronic immune activation in mice that constitutively expressed CD70, the ligand for the tumor necrosis factor receptor family member CD27, on B cells. CD70 transgenic (CD70 Tg) mice showed a progressive conversion of naive T cells into effector-memory cells, which culminated in the depletion of naive T cells from lymph nodes and spleen.

Chemokine receptor expression on T cells is related to new lesion development in multiple sclerosis.

The expression of chemokine receptors CCR5 and CXCR3 on CD4 and CD8 positive T cells in blood, measured by flow cytometry, was studied in 124 patients with different clinical subtypes of multiple sclerosis (MS) and 22 healthy controls. In a subgroup of patients (n=69) from whom MRI was available, chemokine receptor expression was correlated to the annualised changes in T1 and T2 lesion load. It was found that CCR5 and CXCR3 on both cell types might have impact on annualised increase in T2 lesion load, but not on T1 lesion load.

Baseline T cell reactivity in multiple sclerosis is correlated to efficacy of interferon-beta.

Background: Measuring proliferative responses of T lymphocytes is a simple, reproducible and widely used assay of immune competence. Evidence suggests a role of T cell reactivity in autoimmune diseases. Interferon (IFN)-beta blocks in vitro proliferation of human T cells.

Proliferation requirements of cytomegalovirus-specific, effector-type human CD8+ T cells.

Two prototypic types of virus-specific CD8(+) T cells can be found in latently infected individuals: CD45R0(+)CD27(+)CCR7(-) effector-memory, and CD45RA(+)CD27(-)CCR7(-) effector-type cells. It has recently been implied that CD45RA(+)CD27(-)CCR7(-) T cells are terminally differentiated effector cells and as such have lost all proliferative capacity. We show in this study, however, that stimulation of CMV-specific CD45RA(+)CD27(-)CCR7(-) T cells with their cognate peptide in concert with either CD4(+) help or IL-2, IL-15, or IL-21 in fact induces massive clonal expansion.

Expression of the EGF-TM7 receptor CD97 and its ligand CD55 (DAF) in multiple sclerosis.

CD97 is a recently identified seven-span transmembrane (7-TM) protein that is expressed by leukocytes early after activation. CD97 binds to its cellular ligand CD55 (decay accelerating factor), which protects several cell types from complement-mediated damage. The functional consequences of CD97-CD55 binding are largely unknown, but previous data imply that CD97-CD55 interactions play a role in cellular activation, migration, and adhesion under inflammatory conditions.

Primary immune responses to human CMV: a critical role for IFN-gamma-producing CD4+ T cells in protection against CMV disease.

The correlates of protective immunity to disease-inducing viruses in humans remain to be elucidated. We determined the kinetics and characteristics of cytomegalovirus (CMV)-specific CD4(+) and CD8(+) T cells in the course of primary CMV infection in asymptomatic and symptomatic recipients of renal transplants. Specific CD8(+) cytotoxic T lymphocyte (CTL) and antibody responses developed regardless of clinical signs.

Global visual completion of quasi-regular shapes.

The topic of amodal completion has often been investigated by using partly occluded shapes that are regular. In research that has typically been done with displays such as these regular shapes, it has been shown that global aspects of a shape can determine completion. To see how robust these global influences in the completion process are, we investigated quasi-regular shapes, ie shapes with a certain overall regularity but not based on metrical identities.

Prevention of B cell antigen receptor-induced apoptosis by ligation of CD40 occurs downstream of cell cycle regulation.

Cross-linking of the B cell antigen receptor (BCR) on germinal center B cells can induce growth arrest and apoptosis, thereby eliminating potentially autoreactive B cells. Using the Burkitt lymphoma cell line Ramos as a model, we studied the commitment to apoptosis following growth arrest, as well as how triggering of CD40 or addition of tumor necrosis factor (TNF)-alpha can interfere to block cell death. Both BCR triggering and direct induction of growth arrest by sodium butyrate (n-But) caused hypophosphorylation of the retinoblastoma protein (pRb), followed by apoptosis.

CD20-induced B cell death can bypass mitochondria and caspase activation.

The apoptotic pathway activated by chimeric anti-CD20 monoclonal antibodies (rituximab, IDEC.C2B8) was analyzed using the Burkitt lymphoma cell line Ramos. Crosslinking of CD20 (CD20XL) induced apoptosis in Ramos cells, which involved loss of mitochondrial membrane potential (Deltapsi(m)), the release of cytochrome-c (cyt-c), and activation of caspases-9 and -3.