Chronic T lymphoid leukemias are defined as leukemias of post-thymic T
cells. The CD4(+)CD8(+) double-positive (DP) phenotype is seen in a f
ew cases. Since DP generally occurs in thymic T cells, whether the DP
T leukemia cells represent thymic or peripheral T cells has been a mat
ter of controversy. To address this issue, we studied phenotypical fea
tures in eight cases of DP T cell leukemia. Thymic DP T cells and peri
pheral CD8(+) T cells have CD8 of alpha beta subunit, while CD8 alpha
alpha is induced in CD4(+) T cells on activation with IL-4. We found t
hat two patients with DP T large granular lymphocyte leukemia (LGLL) s
howed dim expression of CD8 alpha alpha, identical to the phenotype on
IL-4-activated DP-T cells. The leukemic cells of these patients expre
ssed IL-4 mRNA and produced high levels of IL-4. These findings sugges
t that they may be derived from peripheral CD4(+) T cells. Three patie
nts with adult T cell leukemia/lymphoma (ATLL) showed CD8 alpha alpha,
suggestive of an activated peripheral T cell origin. One case express
ed CD8 alpha alpha dim and IL-4 mRNA, while the other two cases expres
sed no IL-4 mRNA and showed CD8 alpha alpha bright phenotype, features
not found in normal T cell populations. Three patients with T-prolymp
hocytic leukemia (T-PLL) expressed CD8 alpha beta. The DP phenotype is
relatively common in T-PLL, and CD4(+)CD8 alpha beta(+) is characteri
stic 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 th
e late stage of thymic T cell development. On the basis of these findi
ngs, we propose a late thymic origin for on T-PLL. The phenotype of DP
T cells differed for each entity and appeared to correlate with minor
normal DP T cell population.