Peripheral canine CD4+CD8+ double-positive T cells - unique amongst others

T lymphocytes co-expressing CD4 and CD8 (“double-positive T cells”) are commonly associated with a thymic developmental stage of T cells. Their first description in humans and pigs as extrathymic T cells with a memory phenotype almost 30 years ago came as a surprise. Meanwhile peripheral double-positive T cells have been described in a growing number of different species. In this review we highlight novel data from our very recent studies on canine peripheral double-positive T cells which point to unique features of double-positive T cells in the dog. In contrast to porcine CD4+CD8+ T cells forming a homogenous cellular population based on their expression of CD4 and CD8α, canine CD4+CD8+ T cells can be divided into three different cellular subsets with distinct expression levels of CD4 and CD8α. Double-positive T cells expressing CD8β are present in humans and dogs but absent in swine. Moreover, canine CD4+CD8+ T cells can not only develop from CD4+ single-positive T cells but also from CD8+ single-positive T cells. Together, this places canine CD4+CD8+ T cells closer to their human than porcine counterparts since human double-positive T cells also appear to be heterogeneous in their CD4 and CD8α expression and have both CD4+ and CD8+ T cells as progenitor cells. However, CD4+ single-positive T cells are the more potent progenitors for canine double-positive T cells, whereas CD8+ single-positive T cells are more potent progenitors for human double-positive T cells. Canine double-positive T cells have an activated phenotype and may have as yet unrecognized roles in vivo in immunity to infection or in inflammatory diseases such as chronic infection, autoimmunity, allergy, or cancer.