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Biomedical subjects

D van Essen

Publications and source records attributed to D van Essen.

5 recordsLinked to original sources
PubMed1998

T cell-dependent immune response in C1q-deficient mice: defective interferon gamma production by antigen-specific T cells.

The role of the classical complement pathway in humoral immune responses was investigated in gene-targeted C1q-deficient mice (C1qA-/-). Production of antigen-specific immunoglobulin (Ig)G2a and IgG3 in primary and secondary responses to T cell-dependent antigen was significantly reduced, whereas IgM, IgG1, and IgG2b responses were similar in control and C1qA-/- mice. Despite abnormal humoral responses, B cells from C1qA-/- mice proliferated normally to a number of stimuli in vitro. Immune complex localization to follicular dendritic cells within splenic follicles was lacking in C1qA-/- mice. The precursor frequency of antigen-specific T cells was similar in C1qA-/- and wild-type mice. However, analysis of cytokine production by primed T cells in response to keyhole limpet hemocyanin revealed a significant reduction in interferon-gamma production in C1qA-/- mice compared with control mice, whereas interleukin 4 secretion was equivalent. These data suggest that the classical pathway of complement may influence the cytokine profile of antigen-specific T lymphocytes and the subsequent immune response.

Animals↗
PubMed1998

CD40 ligand signals optimize T helper cell cytokine production: role in Th2 development and induction of germinal centers.

The role of CD40 in the development of germinal centers (GC) is not simply to initiate the B cell response, as rudimentary GC can develop in CD40-/- mice that are injected with CD40-immunoglobulin (Ig) fusion protein. This indicates that CD40 ligand (CD40L) transduces a signal to T cells that is important in the process. In this study we have used an in vitro model of GC development to investigate the role of CD40L, cytokines and other co-stimuli. The model involves the specific induction of an H-2E transgene in GC B cells (in Sma58 mice). We find that Th2 cytokines together with Ig and CD40 cross-linking are the most efficient means of induction of the GC phenotype. Although IL-4 plays some inductive role, it is not the sole active ingredient in the mix of cytokines made by Th2 cells. Our studies on primary T cells and T cell clones activated in the absence of CD40 on antigen-presenting cells or CD40L on T cells indicate that the CD40L co-stimulus does not directly bias the response to Th2 cells, as previously reported, but that it augments terminal effector T cell differentiation or the level of secretory activity. However, both in vitro and in vivo, the CD40L co-stimulus is crucially important for Th2 development as in its absence IL-4 production is suboptimal and does not compete with a larger, more rapid IFN-gamma response.

Animals↗
PubMed1997

Observations on memory B-cell development.

We dissect in this article the roles of CD40 and its ligand in memory B-cell formation. Our data indicate that CD40 ligation does not directly lead to GC formation but it plays an indirect role related to maturation of helper T cells; signalling is bidirectional, to B cells, via CD40, upregulating cytokine receptor expression and to T cells, via CD40L, causing secretion of cytokines necessary for GC initiation. Later in the GC, CD40 selects mutated B cells for entry into the memory pool. This second T-cell-mediated CD40 ligation has consequences distinct from the first (rescue versus proliferation) that arise from rewiring of CD40 signal transduction pathways.

Animals↗
PubMed1995

CD40 ligand-transduced co-stimulation of T cells in the development of helper function.

Mice that lack either CD40 (expressed on B cells) or CD40 ligand (expressed on activated T cells) are able neither to make IgG, IgA or IgE antibody responses, nor to generate germinal centres (the sites of formation of memory B cells). It has been assumed that these lesions were the result of an absence of signals to B cells through CD40. Here we show that the failure to signal T cells through CD40 ligand is an important contributory cause. Administration of soluble CD40 in vivo to CD40 knockout mice, restoring the missing signal through CD40 ligand initiates germinal centre formation. Furthermore, T cells primed in the absence of CD40 (in CD40 knockout mice) are unable to help normal B cells to class switch or to form germinal centres (GC). These results indicate that co-stimulation of T cells through CD40 ligand causes their differentiation into cells that help B cells to make mature antibody responses and to generate memory populations.

Animals↗