"The combination of arsenic, interferon-alpha, and zidovudine restores an ""immunocompetent-like"" cytokine expression profile in patients with adult T-cell leukemia lymphoma."
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.
Adult T cell leukemia (ATL) is an aggressive malignancy that is associated with HTLV-I infection and characterized by constitutive expression of the high-affinity interleukin-2 receptor.
A long-term T-cell line, termed SP+, was developed from a human T-cell leukemia virus type I (HTLV-I)-infected patient with adult T-cell leukemia that is dependent on exogenous IL-2 for growth.
Analysis of RNA from HTLV-I-infected cells established from patients with adult T cell leukemia (ATL) as well as tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) and both IL-2-dependent and IL-2-independent HTLV-I-infected cell lines by RNase protection has confirmed the existence of all of the alternatively spliced messages in each cell line analyzed.
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.
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.
BAY 1143572-treated ATL-bearing mice (once daily 12.5 mg/kg oral application) demonstrated significantly decreased ATL cell infiltration of the liver and bone marrow, as well as decreased human soluble interleukin-2 receptor levels in serum (reflecting the ATL tumor burden), compared with untreated mice (n = 8 for both).
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.
Evidence has been provided which suggests the involvement of an aberrant function of the IL-2 system in developing T cell neoplasms, particularly the adult T cell leukemia/lymphoma (ATL).
Expression of human T-cell leukaemia virus type I and associated antigens, and interleukin-2 and receptor in lymph nodes of adult T-cell leukaemia/lymphoma.
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.
Here, we report that IL-2-dependent ATL cell lines also express IL-4Ralpha and respond to IL-4, which was verified by the activation of cytoplasmic transcriptional activator Stat6 protein.
High rate of chromosomal abnormalities in HTLV-I-infected T-cell colonies derived from prodromal phase of adult T-cell leukemia: a study of IL-2-stimulated colony formation in methylcellulose.