Adult T-cell leukemia (ATL) cells have been shown to express the receptor for IL-2 by studies using anti-CD25 monoclonal antibody, but these cells usually show no or only a weak proliferative response to IL-2.
To determine whether the interleukin-2 receptor (IL-2R) beta-chain (p70-75) is expressed on leukemic cells from patients with adult T cell leukemia (ATL) as well as alpha-chain (p55, Tac), we performed radiolabeled interleukin-2 (IL-2) binding assay, chemical crosslinking of radiolabeled IL-2 and flow cytometric analysis using a newly-developed anti-IL-2R beta-chain antibody.
Independently, adult T-cell leukemia-derived factor (ADF) was purified from human T-lymphotropic virus I-infected leukemic T-cell line (ATL-2) and reported as an interleukin 2 (IL-2) receptor-inducing factor.
The transforming activity of tax, possibly via a transcriptional deregulation of cell growth control, may play an important role in leukemogenesis of ATL in addition to its aberrant stimulation of the interleukin 2 system.
Collectively, these results suggest that immune activation in HAM/TSP, in contrast to ATL, is virally driven by the transactivation and coordinate expression of IL-2 and IL-2R alpha.
Flow cytometric analysis demonstrated the expression of the IL-2R beta chain on granular lymphocytes (GLs) from all eight patients with granular lymphocyte proliferative disorders (GLPDs), on adult T-cell leukemia (ATL) cells from all three patients with ATL, and on T-cell acute lymphoblastic leukemia (T-ALL) cells from one of three patients with T-ALL.
Human T cell lymphotropic virus-I (HTLV-I) associated Japanese, Carribean, and sporadic adult T cell leukemia/lymphomas usually express pan-T cell antigens, the CD4+ CD8- phenotype, and various T cell-associated activation antigens, including the interleukin-2 receptor (CD25).
Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2.
Using the clone-specific rearrangement of the T cell receptor gene as the genetic marker of the clonotype, we analyzed the clonal origin of the interleukin 2 (IL-2)-dependent human T-lymphotrophic virus I (HTLV-I)-positive T cell lines established from various adult T cell leukemia (ATL) patients.
To examine the possibility of heterogeneous mechanisms in the proliferation of adult T cell leukemia (ATL) cells, leukemic cells from 13 patients, nine acute-type and four chronic-type ATL, were examined for the production of interleukin 2 (IL 2) with or without mitogenic stimulation and their response to recombinant IL 2 when exogeneously added.
ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover.
The constant display of large numbers of IL-2 receptors which may be aberrant in the ATL cells may play a role in the uncontrolled growth of these leukemic T cells.
However, clonality analysis based on T cell receptor gene rearrangement profiles and the site of HTLV-I provirus integration revealed IL-2-dependent growth in leukemic cells in four patients with ATL.
In HTLV-I transformed T-cell lines established from the patients with adult T-cell leukemia (ATL), there is a constitutive activation of the normal IL-2 receptor (IL-2-R) gene.
As is the case with adult T cell leukemia (ATL)-derived human T cell lines transformed by HTLV-I, these rat cell lines unequivocally expressed interleukin 2 (IL-2) receptor, as determined by radiolabeled IL-2 binding.
Normal resting T-cells and most leukemic T-cell populations do not express IL-2 receptors; however, the leukemic cells of the 11 patients examined who had human T-cell lymphotropic virus-associated adult T-cell leukemia expressed the Tac antigen.
The ability to culture target cells with T-cell growth factor and sensitive detection systems for the virally encoded polymerase reverse transcriptase permitted isolation of HTLV-I, which is strongly linked to the cause of adult T-cell leukemia and associated with other lymphoid malignancies in endemic areas.
Unlike IL 2-independent HTLV-1(+) cell lines that constitutively expressed Il 2-R, the IL 2-R expression on ED cells declined in the absence of crude IL 2 or recombinant IL 2.