The influence of CD25+ cells on the generation of immunity to tumour cell lines in mice.

CD25+ regulatory T cells comprise 5-10% of CD4+ T cells in naïve mice and have been shown in several in vivo murine models to prevent the induction of autoimmune disease and inflammatory disease. Since T cells, which mediate autoimmunity, can through recognition of self-antigens also target tumour cells, it was postulated that CD25+ regulatory cells would also inhibit the generation of immune responses to rumours. Depletion of these cells using CD25-specific monoclonal antibodies has indeed been shown to promote rejection of several transplantable murine tumour cell lines including melanoma, leukaemia and colorectal carcinoma.

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.

The influence of macrophage inflammatory protein-1alpha on protective immunity mediated by antiviral cytotoxic T cells.

Macrophage inflammatory protein 1alpha (MIP-1alpha), a member of the CC-chemokine subfamily, is known to induce chemotaxis of a variety of cell types in vivo. Although the role of MIP-1alpha in inflammatory responses generated following primary infection of mice with many different pathogens has been characterized, the influence of this chemokine on the generation of antigen-specific T-cell responses in vivo is less well understood. This is important, as virus-specific CD8+ T lymphocytes (CTL) play a crucial role in defence against viral infections, both acutely and in the long term.

CD25+ regulatory T cells and tumor immunity.

Tumor cells express a range of antigens including self-antigens (those whose expression is shared by normal host tissue) and non-self antigens (such as those that arise as a result of mutations in normal cellular genes or in the case of some tumors, viral antigens). Immune responses to both types of antigen have been identified in human patients with cancer and in murine tumor models. In both cases, these responses are typically weak and generally fail to result in tumor rejection.