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Emma Jones

Publications and source records attributed to Emma Jones.

23 records · Page 2Linked to original sources
PubMed2002

Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice.

Treatment with monoclonal antibodies (mAbs) specific for CD25 (anti-CD25 mAb) has been shown to suppress growth of a variety of different tumours in mice. These studies did not however determine whether or not anti-CD25 mAbs facilitate tumour rejection by depletion of regulatory T cells or by binding to tumour-specific effector cells. Using a murine model of melanoma we have found that treatment of mice with anti-CD25 mAb facilitates long-term CD4+ T cell-mediated tumour immunity through depletion of CD25+ regulatory cells. We further show that the effector CD4+ T cells confer long-term tumour immunity even in the presence of CD25+ regulatory cells and do not require CD8+ T cells for tumour rejection. The inhibitory impact of anti-CD25 mAb treatment on tumour growth may be the result of depleting CD25+ regulatory cells that normally inhibit the generation of immune responses to self-antigens that are shared by the tumour. We have performed experiments to determine whether or not immune responses to melanocyte antigens are generated in anti-CD25 mAb-treated, melanoma-immune mice. The results of the experiments indicate that a T cell response to the melanocyte antigen tyrosinase accompanies suppression of tumour growth in mice lacking CD25+ regulatory cells.

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PubMed2002

Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens.

Although it is known that the immune system can mount responses to a variety of tumors it is clear that most tumors exhibit weak or even undetectable immunogenicity. Recent findings suggest that the lack of tumor immunogenicity is partly due to a population of cells called CD4+ CD25+ regulatory T cells since depletion of these cells in mice can result in tumor rejection. These cells have also been shown to inhibit the development of organ-specific autoimmune diseases suggesting that they inhibit immune responses to tissue-specific self-antigens. Such immune responses may also mediate tumor rejection. Alternatively, immune responses in mice depleted of regulatory cells may target tumor antigens that are not tissue-specific, but which are shared by tumors of diverse origins. In experiments performed to discriminate between these possibilities we found, using the murine colorectal tumor CT26, that tumor immunity stimulated in the absence of regulatory cells is not restricted to tumors of colorectal origin, but is effective against tumors of different histological types such as B cell lymphomas and a renal cell carcinoma. By comparing this to CT26-induced immunity through the use of adjuvant we show that the generation of cross-reactive tumor immunity is a specific manifestation of CD25+ regulatory cell depletion. The generation of CD4+ T cells capable of mediating tumor rejection is another important feature of tumor immunity induced in the absence of CD25+ cells.

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PubMed2002

Fas ligand breaks tolerance to self-antigens and induces tumor immunity mediated by antibodies.

The role of Fas ligand (FasL) in programmed cell death via interaction with its receptor Fas is well characterized. It has been proposed that expression of FasL can confer immune privilege to some organs, allowing them to kill infiltrating lymphocytes and inflammatory cells. However, a number of studies have shown that when tumors or transplants express FasL, rejection often occurs as a consequence of proinflammatory functions of FasL. Here we demonstrate that FasL elicits tumor immunity in a murine melanoma model with weak immunogenicity and low expression of major histocompatibility complex (MHC) class I. We show that protected mice recognize melanocyte differentiation self-antigens. Importantly, tumor immunity is mediated by antibodies, as it can be transferred by serum from protected mice.

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