High CD70 expression was observed on CD4 + CD25+ T cells from patients with acute-type ATL, while patients with smoldering- or chronic-type ATL and HTLV-1 carriers exhibited lower expression.
Adult T cell leukemia/lymphoma (ATL) is an aggressive cancer of CD4/CD25(+) T lymphocytes, the etiological agent of which is human T-cell lymphotropic virus type 1 (HTLV-1).
Human T-cell leukemia virus (HTLV)-1 is a human retrovirus and the etiological agent of adult T-cell leukemia/lymphoma (ATLL), a fatal malignancy of CD4/CD25+ T lymphocytes.
To identify novel therapeutic targets and diagnostic markers for ATL, we employed focused proteomic profiling of the CD4(+)CD25(+)CCR4(+) T-cell subpopulation in which HTLV-1-infected cells were enriched.
Adult T-cell leukaemia-lymphoma (ATLL) is an aggressive malignancy of CD4(+) CD25(+) T lymphocytes, characterized by a severely compromised immunosystem, in which the human T-cell lymphotropic virus type 1 (HTLV-1) has been recognized as the aetiological agent.
In flow cytometric analysis, the percentages of CD4(+)CADM1(+) double-positive cells correlated well with both the percentages of CD4(+)CD25(+) cells and with abnormal lymphocytes in the peripheral blood of patients with various types of ATLL.
In the present study, we show that an IκB kinase 2 (IKK2) inhibitor, IMD-0354, efficiently inhibits the survival of CD4(+) CD25(+) primary ATL cells and prevents the growth of or induces apoptosis of patient-derived ATL cell lines.
Antibody therapy against ATL was initially started with interleukin-2 receptor α-subunit, CD25, as a target molecule in the late 1980s, and is currently ongoing.
Furthermore, the capacity of ATLL cells to suppress proliferation of heterologous CD4(+)CD25(-) cells correlated with the frequency of CD4(+) FoxP3(+) cells but was independent of CD25 expression.
Leukemic (ATL) T cells constitutively expressing CD25 were characteristic of heterogeneous Foxp3 expression, such as intra- and inter-case heterogeneity in intensity, inconsistency with CD25 expression, and a discrepancy in the mRNA and its protein expression.
Since most ATLL cells express both CD4 and CD25, these tumors might originate from CD4(+)CD25(+)FOXP3(+) Treg cells, based on their phenotypic characteristics.
Comparisons of the transcriptional and translational levels of interleukin-2 receptor alpha chain (IL-2R alpha), transforming growth factor-beta 1 (TGF-beta 1) and intracellular adhesion molecule-1 (ICAM-1) in ATL, HAM/TSP, and SPC and in several control populations revealed selectively up-regulated expression in ATL.
A polymerase chain reaction (PCR) method was used to detect the interleukin-2 receptor alpha-chain (IL-2R alpha) chain which lacks the conventional transmembrane (TM) domain in mRNA from human T-cell leukaemia virus type-I (HTLV-I)-infected cell lines or peripheral blood mononuclear cells (PBMC) isolated from adult T-cell leukaemia (ATL) patients.
The surface phenotype showed that both the original leukemic cells and the WHN2 cells had a common phenotype of ATL, i.e., positive for CD2, CD4, human leukocyte antigen DR (HLA-DR) and CD25, but negative for CD8, a characteristic of helper/inducer T-cells.
The tumor cells represented outgrowth of the original ATL leukemic clone in that they had monoclonal or oligoclonal integrations of the HTLV-I provirus identical to the leukemic clone and predominantly expressed the cell surface markers, CD4 and CD25.
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.
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).
Normal resting T cells and most leukemic T-cell populations examined did not express IL-2 receptors; however, the leukemic cells of all patients with human T-cell lymphotrophic virus (HTLV-I)-associated adult T-cell leukemia (ATL) expressed the Tac antigen.
The expression of Tac antigen, investigated in 27 cases of human T cell leukemia virus I-negative chronic T cell leukemia, which included the 15 cases of T-PLL, showed a good correlation with abnormalities of 7q35.
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.