Double-negative (CD4^- CD8^-) T cells from adult T-cell leukemia patients also have poor expression of the T-cell receptor αβ/CD3 complex

We present four patients with adult T-cell leukemia (ATL) derived from a novel T-cell subset (CD4^-, CD8^- [double-negative, DN], T-cell receptor [TCR] αβ⁺). In the ATL cells of these patients, neither gene nor surface expression of CD4 and CD8 antigens was detected. Clinical and laboratory data showed no difference between DN-ATL and CD4⁺ATL patients. In contrast to typical CD4⁺ATL cells, DN-ATL cells were shown to express the protein and messenger RNA (mRNA) for S100β in immunocytochemical assay and the reverse- transcription polymerase chain reaction assay. The mean fluorescence intensity of the TCR/CD3 complex was extremely low in all four DN-ATL patients as well as in typical CD4⁺ ATL. All four patients had TCR β and γ chain gene rearrangements, with deletion of TCR δ chain gene and mRNA expression for TCR α, β, and CD3 δ but not for TCR γ and δ chain genes. Thus, CD4^- CD8^- TCR αβ T cells are also a target for human T-cell lymphotropic virus type I-induced leukemogenesis. In addition, expression of the TCR αβ/CD3 complex on the DN-ATL cells was further diminished by the addition of anti-CD3 or anti-TCR αβ monoclonal antibody. These results suggest that the decreased expression of the TCR αβ/CD3 complex by ATL cells plays a key role in the development of ATL, irrespective of CD4 expression.