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Antigen Doses (antigen + dose)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

CD4+ T-cell memory: generation and multi-faceted roles for CD4+ T cells in protective immunity to influenza

IMMUNOLOGICAL REVIEWS, Issue 1 2006
Susan L. Swain
Summary:, We have outlined the carefully orchestrated process of CD4+ T-cell differentiation from naïve to effector and from effector to memory cells with a focus on how these processes can be studied in vivo in responses to pathogen infection. We emphasize that the regulatory factors that determine the quality and quantity of the effector and memory cells generated include (i) the antigen dose during the initial T-cell interaction with antigen-presenting cells; (ii) the dose and duration of repeated interactions; and (iii) the milieu of inflammatory and growth cytokines that responding CD4+ T cells encounter. We suggest that heterogeneity in these regulatory factors leads to the generation of a spectrum of effectors with different functional attributes. Furthermore, we suggest that it is the presence of effectors at different stages along a pathway of progressive linear differentiation that leads to a related spectrum of memory cells. Our studies particularly highlight the multifaceted roles of CD4+ effector and memory T cells in protective responses to influenza infection and support the concept that efficient priming of CD4+ T cells that react to shared influenza proteins could contribute greatly to vaccine strategies for influenza. [source]

Establishment and recall of CD8+ T-cell memory in a model of localized transient infection

IMMUNOLOGICAL REVIEWS, Issue 1 2006
Katherine Kedzierska
Summary:, The influenza A virus model of localized, transient respiratory infection provides a well-defined experimental system for dissecting the induction and maintenance of CD8+ T-cell memory. This review focuses on quantitative and qualitative aspects of the prominent DbNP366 - and DbPA224 -specific CD8+ T-cell responses in virus-infected B6 mice. The different virus-specific effector and memory sets are compared by phenotypic [CD62L, interleukin-7 receptor-, (IL-7R,), and IL-15R, expression] and functional [interferon-, (IFN-,), tumor necrosis factor-, (TNF-,), and IL-2 production] analyses. Most clonotypes [defined by T-cell receptor (TCR) CDR3, sequence] generated during the acute phase of infection survive into memory, with those expressing the more consensus ,canonical' TCRs being the major contributors to the recall response. The extent of clonal expansion and the size of memory CD8+ T-cell populations has been characterized for mice challenged with either wildtype or mutant viruses, where broadly equivalent DbNP366 and DbPA224 expression was achieved by disabling the peptides in their native configuration, then expressing them in the viral neuraminidase protein. Combining the clonotypic and antigen dose analyses led to a somewhat mechanistic conclusion that the magnitude of any virus-specific CD8+ T-cell response will be a direct function of antigen dose and the size of the naïve or memory CD8+ T-cell precursor pool. [source]

Proximal changes in signal transduction that modify CD8+ T cell responsiveness in vivo

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2003
Séverine Guillaume
Abstract The antigen dose conditions the functional properties of CD8+ T cells generated after priming. At relatively low antigen doses, efficient memory T cells may be generated, while high antigen doses lead to tolerance. To determine the mechanisms leading to such different functional outcomes, we compared the proximal TCR signal transduction of naive cells, to that of memory or high-dose tolerant cells generated in vivo. In vivo activation led to the constitutive phosphorylation of CD3,, recruiting Zap70, in both memory and tolerant cells. In tolerant cells, these phenomena were much more marked, the CD3, and , chains no longer associated, and the Src kinases p56Lck and p59Fyn were inactive. Therefore, when the antigen load overcomes the capacities of immune control, a new mechanism intervenes to block signal transduction: the recruitment of Zap70 to CD3, becomes excessive, leading to TCR complex destabilization, Src kinase dysfunction, and signal arrest. [source]

Antigen dose-dependent suppression of murine IgE responses is mediated by CD4,CD8, double-negative T cells

CLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2010
C. Barwig
Summary Background The IgE response against protein antigens is profoundly influenced by the dose used for sensitization. Objective The aim of the study was to identify immune cells that are involved in antigen dose-dependent regulation of IgE formation. Methods Wild-type mice as well as T helper (Th)1-deficient IL-12p40,/, and IFN-,,/, mice were immunized by repeated intraperitoneal injection of either low doses (K01 mice) or high doses (K100 mice) of keyhole limpet haemocyanin adsorbed to aluminium hydroxide. Splenocytes of immunized mice were restimulated in vitro and antigen-dependent T cell proliferation and cytokine production were measured. The frequency of regulatory T cell subsets among splenocytes from K01 and K100 mice was compared using fluorocytometry and RT-PCR analysis. Splenocytes or T cell subpopulations were transferred into naïve mice and the effect of lymphocyte transfer on IgE production after priming of recipients with low antigen doses was determined. Results Specific IgE production was considerably impaired in K100 mice. Antigenic restimulation revealed hypoproliferation of K100 splenocytes and reduced production of Th2 cytokines IL-4, IL-5 and IL-13, but no induction of IFN-, production. Moreover, lymphocytes from K01 and K100 mice did not show significant differences in the expression of molecules associated with the phenotype or activity of conventional regulatory T cells. Transfer of splenocytes or purified T cells from K100 mice substantially suppressed the induction of IgE production in the recipients in an antigen- and isotype-specific manner. Neither CD4+ nor CD8+ T cells from K100 mice were able to inhibit IgE formation; instead, we identified CD4,CD8, double-negative T cells (dnT cells) as the principal T cell population, which potently suppressed IgE production. Conclusion Our data demonstrate that CD4,CD8, dnT cells play a major role in the regulation of IgE responses induced by high antigen doses. [source]