TROUBLESOME T CELLS: THE ROLE OF REGULATORY T CELLS IN DOGS WITH CANCER

摘要

Treg are a distinct subset of T cells that comprise between 5 - 8% of the total population of T cells in the normal mouse or human lymph node, or 10 - 12% of the total CD4~+ population (1, 2). Treg directly suppress the proliferation of harmful self-reactive T cells and play a critical role in prevention of autoimmune disease and maintenance of peripheral tolerance (2, 3). In mice, humans and cats, Treg can be identified based on surface expression of high levels of the IL-2-receptor-alpha chain (CD25) (4). Although other cell surface molecules such as glucocorticoid-induced TNF-receptor (GITR), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and CD 103 aid in Treg identification, definitive delineation from activated CD4~+ non-regulatory T cells using cell surface marker expression alone is not possible (5 - 7). Recently, however, intracellular detection of the transcription factor FoxP3 has been shown to uniquely identify the murine and human Treg populations (8 - 10). Identification of CD4~+/FoxP3~+ T cells permit distinction of Treg from activated non-regulatory CD4~+ T cells and has greatly facilitated the study of Treg in various diseases such as cancer and autoimmune disorders. We have recently reported the detection of canine Treg using a flow cytometry-based assay that employs a cross-reactive anti-mouse-Foxp3 antibody and an anti-dog-CD4 antibody to identify FoxP3~+/CD4~+ T cells (11). Figure 1 gives representative dot plots of FoxP3 expression by CD4+ T cells (the cell populationin the upper right quadrant of each plot) from the blood (A), an uninvolved lymph node (B), and a rumor-draining lymph node (C) in a dog with an oral melanoma. In (D), staining of blood from the same dog with an irrelevant isotype-matched antibody (control for FoxP3 staining) is shown. The percentages of lymphocytes contained within each quadrant are also given for comparison. Using this technique we are investigating the role of Treg in dogs with different types of cancer.