Analysis of canine peripheral CD4+CD8+ double-positive T cell phenotype and function

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T lymphocytes co-expressing CD4 and CD8 (termed double-positive T cells, dp T cells) are commonly associated with a thymic developmental stage of T cells. The first description of dp T cells as extrathymic T cells almost 30 years ago came as a surprise. Peripheral dp T cells have been characterized best in humans and swine. In our very recent studies on canine peripheral dp T cells we unraveled unique features of dp T cells present in dogs but not in swine or humans. Canine CD4+CD8+ T cells can be divided into three different cellular subsets with distinct functional profiles (e.g., production of interferon-gamma), distinct progenitors (CD4+ as well as CD8+ single-positive T cells), distinct expression of markers indicative of effector vs. memory status, or of cytotoxic or regulatory function. The objectives of this proposal are to (i) complete the functional analysis, (ii) complete the characterization of the tissue distribution (lymphatic tissue vs. non-lymphatic tissue) with an emphasis on intestinal mucosal dp T cells, (iii) define subset-specific transcription factors responsible for regulation of CD4 or CD8, and (iv) analyze the in vivo role of dp T cells in a frequent chronic canine inflammatory disease such as idiopathic inflammatory bowel disease.