Possible origin of adult T‐cell leukemia/lymphoma cells from human T lymphotropic virus type‐1‐infected regulatory T cells

Adult T‐cell leukemia/lymphoma (ATLL) is a lymphoproliferative disorder caused by human T lymphotropic virus type 1 (HTLV‐I). Although ATLL cells display an activated helper/inducer T‐cell phenotype, CD4+ and CD25+, they are known to exhibit strong immunosuppressive activity. As regulatory T cells (Treg cells) express CD4+ and CD25+ molecules and possess potent immune response suppressive activity, we investigated a possible link between ATLL cells and Treg cells. In primary ATLL cells, the expression levels of the Treg cell marker molecules Foxp3 and glucocorticoid‐induced tumor necrosis factor receptor family related protein (GITR) were significantly higher than in those from healthy adults. Furthermore, ATLL cells are unresponsive in vitro to concanavalin A stimulation and suppress the proliferation of normal T cells. GITR mRNA expression was induced by the HTLV‐I transactivator Tax, and GITR promoter analyses revealed that this induction depends on the κB site from −431 bp to −444 bp upstream of the putative transcription site. Taken together, ATLL cells may originate from HTLV‐I‐infected Treg cells, and GITR seems to be involved in the progression to ATLL. (Cancer Sci 2005; 96: 527–533)

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