Phenotypical heterogeneity of CD4⁺CD8⁺ double-positive chronic T lymphoid leukemia

Abstract

Chronic T lymphoid leukemias are defined as leukemias of post-thymic T cells. The CD4⁺CD8⁺ double-positive (DP) phenotype is seen in a few cases. Since DP generally occurs in thymic T cells, whether the DP T leukemia cells represent thymic or peripheral T cells has been a matter of controversy. To address this issue, we studied phenotypical features in eight cases of DP T cell leukemia. Thymic DP T cells and peripheral CD8⁺ T cells have CD8 of αβ subunit, while CD8αα is induced in CD4⁺ T cells on activation with IL-4. We found that two patients with DP T large granular lymphocyte leukemia (LGLL) showed dim expression of CD8αα, identical to the phenotype on IL-4-activated DP-T cells. The leukemic cells of these patients expressed IL-4 mRNA and produced high levels of IL-4. These findings suggest that they may be derived from peripheral CD4⁺ T cells. Three patients with adult T cell leukemia/lymphoma (ATLL) showed CD8αα, suggestive of an activated peripheral T cell origin. One case expressed CD8αα dim and IL-4 mRNA, while the other two cases expressed no IL-4 mRNA and showed CD8αα bright phenotype, features not found in normal T cell populations. Three patients with T-prolymphocytic leukemia (T-PLL) expressed CD8αα. The DP phenotype is relatively common in T-PLL, and CD4⁺CD8αβ⁺ is characteristic of thymic T cells. The DP T-PLL cells did not express TdT,CD1 or recombination activating gene-1 (RAG-1), which is down-regulated at the late stage of thymic T cell development. On the basis of these findings, we propose a late thymic origin for DP T-PLL. The phenotype of DP T cells differed for each entity and appeared to correlate with minor normal DP T cell population.