Biomedical subjects

C Asseman

Publications and source records attributed to C Asseman.

9 recordsLinked to original sources

PubMed2002

About CD4pos CD25pos regulatory cells.

Autoreactive cells that escape from thymic negative selection are either anergized or counter-regulated in the peripheral lymphoid organs by regulatory T (Treg) cells. Most investigated Treg cells are CD4pos cells expressing the alpha chain of the IL-2 receptor (CD25). Absence of this particular population leads to the development of a wide range of autoimmune disorders, suggesting a critical role for CD4pos CD25pos cells in the maintenance of normal immune homeostasis. Numerous studies have aimed at unraveling the mechanisms of regulation, focusing mainly on naturally occurring Treg cells (generated in naive animals) and regulation of CD4pos autoreactive cells. In contrast, generation following antigenic priming of CD4pos CD25pos Treg cells with non-self (viral) antigen specificity and regulation of virus-activated CD4pos and CD8pos cells remain to be investigated. In this review, we describe the data collected over the past few years of intense focus on CD4pos CD25pos Treg cells and present our approach to investigate the generation of antigen-specific Treg cells during the course of an anti-viral immune response.

Animals↗

PubMed2001

Control of intestinal inflammation by regulatory T cells.

Transfer of CD4+ T cells to immune-deficient mice in the absence of the CD25+ subset leads to the development of colitis, indicating that regulatory cells capable of controlling a bacteria-driven inflammatory response are present in normal mice. Cells with this function are present in the thymus as well as in the periphery of germ-free mice, suggesting they may be reactive with self-antigen. These cells resemble CD4+CD25+ cells that inhibit organ-specific autoimmunity, suggesting that a similar subset of regulatory T cells may control responses to self and foreign antigens. Development of colitis is dependent on accumulation of activated CD134L+ dendritic cells (DC) in the mesenteric lymph nodes, which is inhibited by CD4+CD25+ cells, indicating that regulatory T cells may control DC activation in vivo. Whilst inhibition of T-cell activation in vitro by CD4+CD25+ cells does not involve interleukin-10 and transforming growth factor-beta, these cytokines are required for the suppression of colitis. It may be that control of responses that activate the innate immune system requires multiple mechanisms of immune suppression. Recently, we identified CD4+CD25+ cells with immune suppressive activity in the thymus and peripheral blood of humans, raising the possibility that dysfunction in this mechanism of immune regulation may be involved in the development of autoimmune and inflammatory diseases.

ADP-ribosyl Cyclase↗

PubMed2000

Control of experimental inflammatory bowel disease by regulatory T cells.

A helper T cell type 1-mediated colitis driven by enteric bacteria develops in severe combined immunodeficient mice after transfer of CD45RB(high)CD4(+) T cells. Development of disease can be prevented by cotransfer of the reciprocal CD45RB(low) subset. Analysis of the mechanism of immune suppression transferred by CD45RB(low)CD4(+) cells revealed essential roles for both IL-10 and TGF-beta. These data indicate that a functionally specialized population of regulatory T (Treg) cells exists in normal mice and that these can prevent the development of pathogenic responses toward commensal bacteria. The role of Treg cells in the control of the immune response is discussed.

Adoptive Transfer↗

PubMed1999

An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation.

A T helper cell type 1-mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RB(high) CD4(+) T cells and can be prevented by cotransfer of the CD45RB(low) subset. The immune-suppressive activities of the CD45RB(low) T cell population can be reversed in vivo by administration of an anti-transforming growth factor beta antibody. Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RB(low) population. This population isolated from IL-10-deficient (IL-10(-/-)) mice was unable to protect from colitis and when transferred alone to immune-deficient recipients induced colitis. Treatment with an anti-murine IL-10 receptor monoclonal antibody abrogated inhibition of colitis mediated by wild-type (WT) CD45RB(low) CD4(+) cells, suggesting that IL-10 was necessary for the effector function of the regulatory T cell population. Inhibition of colitis by WT regulatory T cells was not dependent on IL-10 production by progeny of the CD45RB(high) CD4(+) cells, as CD45RB(low) CD4(+) cells from WT mice were able to inhibit colitis induced by IL-10(-/-) CD45RB(high) CD4(+) cells. These findings provide the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens.

Animals↗

PubMed1998

CD38+ CD45RB(low) CD4+ T cells: a population of T cells with immune regulatory activities in vitro.

An antibody reactive with CD38 revealed both phenotypic and functional heterogeneity amongst CD45RB(low) cells. Functional analysis of the CD38+ and CD38- fractions showed that the latter contained T cells which responded to recall antigens and produced high levels of cytokine in response to polyclonal stimulation. In contrast, the CD38+ population failed to proliferate or to produce detectable levels of cytokines. Despite appearing unresponsive, the CD38+ population significantly inhibited anti-CD3-induced proliferation and cytokine secretion by the reciprocal CD38- population. Immune suppression required stimulation through the TCR and was dependent on a physical interaction between regulatory and responding CD4+ populations. It did not involve killing of the responding T cells or secretion of IL-10 or TGF-beta. Despite some similarities there is no direct correlation between the in vitro suppression characteristic of the CD38+ CD45RB(low) subset and in vivo suppression which has been shown to be mediated by unseparated CD45RB(low) CD4+ T cells. However, these results demonstrate that two functionally distinct subsets of T cells reside within the antigen-exposed or CD45RB(low) CD4+ T cell population and are thus generated in vivo: (1) conventional memory T cells which proliferate and secrete cytokines in response to activation and (2) a population of regulatory T cells which inhibit T cell activation in vitro. Antibodies reactive with CD38 may provide a useful tool with which to study the role of these T cell subsets in the induction and regulation of the immune response.

ADP-ribosyl Cyclase↗

PubMed1998

Interleukin 10 is a growth factor for a population of regulatory T cells.

Induction and maintenance of peripheral tolerance are important mechanisms to maintain the balance of the immune system. In addition to the deletion of T cells and their failure to respond in certain circumstances, active suppression mediated by T cells or T-cell factors has been proposed as a mechanism for maintaining peripheral tolerance. However, the inability to isolate and clone regulatory T cells involved in antigen-specific inhibition of immune responses has made it difficult to understand the mechanisms underlying such suppression. Here, we show that chronic activation of both human and murine CD4+ T cells in the presence of interleukin (IL)-10 gives rise to CD4+ T-cell clones with low proliferative capacity, producing high levels of IL-10, low levels of IL-2 and no IL-4. These antigen-specific T-cell clones suppress the proliferation of CD4+ T cells in response to antigen, and prevent colitis induced in SCID mice by pathogenic CD4+CD45RBhigh splenic T cells. Thus IL-10 drives the generation of a CD4+ T-cell subset, designated T regulatory cells 1 (Tr1), which suppresses antigen-specific immune responses and actively downregulates a pathological immune response in vivo.

Animals↗

PubMed1996

Schistosoma mansoni-infected mice show augmented hepatic fibrosis and selective inhibition of liver cytokine production after treatment with anti-NK1.1 antibodies.

Gamma interferon (IFN-gamma) plays an immunoregulatory role at different stages of the experimental Schistosoma mansoni-driven processes in mice through its ability to induce cell cytotoxicity against the parasite larvae and to reduce established hepatic fibrosis. The role of Natural Killer (NK) cells, as possible major source of IFN-gamma, has never been studied during the entire course of murine schistosomiasis. In this paper, we investigated the consequences of in vivo NK cell depletion, maintained during 17 weeks of infection, on both hepatic granuloma development and immunological parameters. We found that NK cell depletion following anti-NK1.1 monoclonal antibody (mAb) injections led to an increase of hepatic collagen content in the late stages of granuloma formation and to the diminution of interleukin 12 (IL-12) p40 and IL-7 mRNA expression in the livers. The hepatic mRNA expression of other cytokines (IFN-gamma, tumor necrosis factor alpha [TNF-alpha] and IL-4), as well as humoral and cytokine responses in sera, were not significantly different between control monoclonal antibody (CmAb) and anti-NK1.1-treated mice. Thus, we demonstrate that the anti-NK1.1 treatment might induce alterations of regulatory mechanisms, detectable at a late stage of a chronic process in immunocompetent mice.

Animals↗

PubMed1996

Cellular immune response and pathology in schistosomiasis.

In the present review, some aspects of the cellular response following the murine Schistosoma mansoni infection are described. Due to the peculiar route used by the schistosome to infect its definitive host, the skin appears as a critical site in which the initial events of the host/parasite relationship occur and where the immune response is initiated. Moreover, the induction and the modulation of the granuloma formation, which represent the main aspect of the pathology of this parasitic disease, is under the control of several cellular populations n which CD4 and CD8 T cells play a key role. The cytokines produced in response to the parasite, such as IL7 in the skin and IFN gamma in the liver, seem to influence the further development of immunity against Schistosoma mansoni.

Animals↗

PubMed1994

A radioimmunoassay for the quantification of human ubiquitin in biological fluids: application to parasitic and allergic diseases.

Purified ubiquitin has been shown to share similar biological and physicochemical properties with a previously characterized lymphokine, platelet activity suppressive lymphokine (PASL). This lymphokine, which inhibits the cytotoxic function of activated platelets, is produced during schistosomiasis and Hymenoptera venom hypersensitivity (HVH). We have developed a radioimmunoassay specific for ubiquitin, in order to determine the ubiquitin levels in human sera and plasma from patients with these pathologies. The working range of the assay was between 60 and 500 ng/ml, and the sensitivity was 8-10 ng/ml. The reproducibility, specificity and accuracy were determined under standard condition (PBS-0.3% BSA) and using different biological fluids (human serum, plasma and T lymphocyte supernatant). Using this assay, we found that the ubiquitin concentrations were higher in both schistosomiasis and HVH (up to 150-300 ng/ml) compared with sera and plasma from healthy donors where the ubiquitin levels did not exceed 50 ng/ml.

Anaphylaxis↗