Immunological Aspects of Adult T-Cell Leukemia/Lymphoma (ATLL), a Possible Neoplasm of Regulatory T-Cells

Adult T-cell leukemia/lymphoma (ATLL) is a distinct disease caused by the first discovered human oncogenic retrovirus, human T-cell leukemia virus type-1 (HTLV-1). The peculiarity of this disease is not only in its causative agent HTLV-1 but also in the character of leukemia cells. ATLL cells express the mature helper/inducer T-cell antigens, CD2, CD3, CD4 and CD5 but usually lacking CD8. Despite CD4 expression, it has long been known that ATLL cells exhibit strong immunosuppressive activity in vitro. Notably, ATLL patients are in severely immunosuppressed conditions and this causes higher incidences of opportunistic infections than other types of leukemia and lymphoma. Since ATLL cells constitutively express CD25, this prompted investigators to study ATLL cells from the viewpoint of regulatory T cells (Treg cells). ATLL cells satisfy all the criteria of Treg cells, as they express Foxp3, the master gene of Treg lineage, the glucocorticoid-induced TNF receptor (GITR), and the cytotoxic T-lymphocyte associated molecul-4 (CTLA-4). Moreover, other profiles including chemokine receptor expression also support that ATLL is a neoplasm of Treg cell origin. Here we review the immunological aspects of ATLL cells and discuss this cell origin.