Biomedical subjects

Amy E Juedes

Publications and source records attributed to Amy E Juedes.

5 recordsLinked to original sources

PubMed2005

Immunomodulatory dendritic cells require autologous serum to circumvent nonspecific immunosuppressive activity in vivo.

In immunotherapy, dendritic cells (DCs) can be used as powerful antigen-presenting cells to enhance or suppress antigen-specific immunity upon in vivo transfer in mice or humans. However, to generate sufficient numbers of DCs, most protocols include an ex vivo culture step, wherein the cells are exposed to heterologous serum and/or antigenic stimuli. In mouse models of virus infection and virus-induced autoimmunity, we tested how heterologous serum affects the immunomodulatory capacity of immature DCs generated in the presence of IL-10 by comparing fetal bovine serum (FBS)- or normal mouse serum (NMS)-supplemented DC cultures. We show that FBS-exposed DCs induce a systemic immune deviation characterized by reduction of virus-specific T cells, delayed viral clearance, and enhanced systemic production of interleukin 4 (IL-4), IL-5, and IL-10 to FBS-derived antigens, including bovine serum albumin (BSA). By contrast, DCs generated in NMS-supplemented cultures modulated immunity and autoimmunity in an antigen-specific fashion. These cells did not induce systemic IL-4, IL-5, or IL-10 production and inhibited generation of virus-specific T cells or autoimmunity only if pulsed with a viral antigen. These data underscore the importance of using autologous serum-derived immature DCs in preclinical animal studies to accurately assess their immunomodulatory potential in future human therapeutic settings, where application of FBS is not feasible.

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PubMed2004

T-bet controls autoaggressive CD8 lymphocyte responses in type 1 diabetes.

The T-box transcription factor T-bet is known to control lineage commitment and interferon-gamma production by T helper 1 (Th1) CD4 lymphocytes. We report here that T-bet is essential for development of CD8 lymphocyte-dependent autoimmune diabetes (type 1 diabetes [T1D]) in the rat insulin promoter-lymphocytic choriomeningitis virus (LCMV) transgenic model for virally induced T1D. In the absence of T-bet, autoaggressive (anti-LCMV) CD8 lymphocytes were reduced in number and produced less IFN-gamma, but increased IL-2 compared with controls. Further analysis showed that T-bet intrinsically controls the generation, but not apoptosis, maintenance, or secondary expansion of antiviral effector/memory CD8 lymphocytes. This observation points toward a therapeutic opportunity for the treatment of T1D and other autoimmune disorders.

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PubMed2003

Helicobacter-induced chronic active lymphoid aggregates have characteristics of tertiary lymphoid tissue.

Susceptible strains of mice that are naturally or experimentally infected with murine intestinal helicobacter species develop hepatic inflammatory lesions that have previously been described as chronic active hepatitis. The inflammatory infiltrates in some models of chronic autoimmunity or inflammation resemble tertiary lymphoid organs hypothesized to arise by a process termed lymphoid organ neogenesis. To determine whether hepatic inflammation caused by infection with helicobacter could give rise to tertiary lymphoid organs, we used fluorescence-activated cell sorting, immunohistochemistry, and in situ hybridization techniques to identify specific components characteristic of lymphoid organs in liver tissue sections and liver cell suspensions from helicobacter-infected mice. Small venules (high endothelial venules [HEVs]) in inflammatory lesions in Helicobacter species-infected livers were positive for peripheral node addressin. Mucosal addressin cell adhesion molecule also stained HEVs and cells with a staining pattern consistent with scattered stromal cells. The chemokines SLC (CCL 21) and BLC (CXCL13) were present, as were B220-positive B cells and T cells. The latter included a naïve (CD45lo-CD62Lhi) population. These findings suggest that helicobacter-induced chronic active hepatitis arises through the process of lymphoid organ neogenesis.

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PubMed2003

Using regulatory APCs to induce/maintain tolerance.

It is well established that antigen-presenting cells (APCs) such as dendritic cells (DCs) possess potent immune-stimulatory function. They are considered to be the key driving element for most immune, autoimmune, and host-defense responses. However, recent evidence suggests that as much as APCs can turn things on, they also have the capability to turn things off. To summarize the evidence for such regulatory function of APCs is the purpose of this review article. We are just beginning to understand whether regulatory APC function can be mapped to a separate lineage of APCs or whether it is more commonly acquired under certain maturation conditions. Furthermore, it becomes apparent that it is important to consider differences between human and mouse DCs as well as splenic-, lymph node-, or blood-derived APCs. We believe that, in the upcoming years, better understanding of positive and negative roles of APCs in immune regulation will benefit both sides of APC therapy: their use in enhancing immunity, for example, in vaccine design and cancer, as well as their application for the treatment of autoimmunity.

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PubMedDate not supplied

Regulatory T-cells in type 1 diabetes.

Type 1 diabetes is a T-cell-mediated autoimmune disease, resulting in destruction of the insulin-producing beta cells in the pancreas. Disease progression is thought to involve the action of T-cells, particularly those producing Th1-type cytokines. Given the complexity in understanding the precise etiology of autoimmune diseases, the diversity of autoantigens, and the variability that exists between individual patients, it might be very difficult to eliminate autoaggressive T-cell responses without resorting to generalized means of immunosuppression. However, recent evidence shows that autoimmune processes are composed not only of autoaggressive T-cell responses but also of autoreactive regulatory components. Enhancing regulatory T-cell responses, therefore, has become an area of intense focus as a means of treating autoimmune diseases like type 1 diabetes. This review will concentrate on two different types of regulatory T-cells, the naturally occurring ('professional') CD4+CD25+ T-cells and antigen-induced ('adaptive') CD4+ Th2-like regulatory T-cells.

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