Functional and phenotypic comparison of human T cell leukemia/lymphoma virus positive adult T cell leukemia with human T cell leukemia/lymphoma virus negative Sézary leukemia, and their distinction using anti-Tac. Monoclonal antibody identifying the human receptor for T cell growth factor.

Abstract

As bstract. Adult T cell leukemia (ATL) and Sezary leukemia are malignant proliferations of T lymphocytes that share similar cell morphology and clinical features. ATL is associated with HTLV (human T cell leukemia/lymphoma virus), a unique human type C retrovirus, whereas most patients with the Sezary syndrome do not have antibodies to this virus. Leukemic cells of both groups were ofthe T3, T4-positive, T8-negative phenotype. Despite the similar phenotype, HTLV-negative S&ary leukemic cells frequently functioned as helper cells, whereas some HTLV-positive ATL and HTLV-positive Sezary cells appeared to function as suppressors of immunoglobulin synthesis. One can distinguish the HTLVpositive from the HTLV-negative leukemias using a monoclonal antibody (anti-Tac) that appears to identify the human receptor for T cell growth factor (TCGF). Resting normal T cells and most HTLV-negative Sezary cells were Tac-negative, whereas all ATL cell populations were Tac-positive. The observation that ATL cells manifest TCGF receptors suggests the possibility that an abnormality of the TCGF-TCGF receptor system may partially explain the uncontrolled growth of these cells.

Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells.

“…Popovic et al (14) also noted the strong expression of Tac Ag on cord blood cells that were transformed by co-culturing with HTLV-producing cell lines. A recent report by Waldmann et al also showed that HTLV-positive ATL cells, but not HTLV-negative Sezary cells, express IL-2 receptors (15). In addition, we found that Tac Ag on ATL cells, unlike those on normal activated T cells, is not modulated by anti-Tac antibody (16), which suggests the abnormal regulation of Tac Ag expression in ATL cells.…”

Functional and phenotypic studies of Japanese adult T cell leukemia cells.

“…One possibility is that ATL cells express IL-2 receptors that can bind IL-2 present in the media, which can result in suppression of T cell dependent immunoglobulin synthesis. In other studies (39,40,42), they needed higher proportions of leukemic cells and higher ratios of leukemic cells to B cells for suppression of PWM-induced Ig synthesis, which is in contrast to our assay system, in which we used a low number of leukemic cells and a low leukemic cell to B cell ratio. In this regard, it has been shown that antigen specific helper T cell clones provide optimal help at low numbers of T4+ cells, but at larger numbers of T4 clones they can inhibit specific antibody production (43).…”

90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

“…The current study used daclizumab (humanized anti-Tac, i.e., anti-CD25; Zenapax) armed with the energetic β-particle emitter 90 Y. Daclizumab targets the 55-kDa IL-2Rα (CD25) subunit that is constitutively expressed on Treg cells but not on other resting normal cells (18,34). In contrast, CD25 is overexpressed on certain lymphoid malignancies, on activated T cells involved in autoimmune disorders, and in allograft rejection (16)(17)(18)(19)(20)(21)(22)34). Increased CD25 expression has been demonstrated in anaplastic large-cell lymphoma, adult T-cell leukemia (ATL)/lymphoma, chronic lymphocytic leukemia, cutaneous T-cell lymphoma, hairy cell leukemia, some B-cell non-Hodgkin's lymphomas, and HL (16)(17)(18)(19)(20)(21)(22)(23)(24)35).…”

“…In contrast, CD25 is overexpressed on certain lymphoid malignancies, on activated T cells involved in autoimmune disorders, and in allograft rejection (16)(17)(18)(19)(20)(21)(22)34). Increased CD25 expression has been demonstrated in anaplastic large-cell lymphoma, adult T-cell leukemia (ATL)/lymphoma, chronic lymphocytic leukemia, cutaneous T-cell lymphoma, hairy cell leukemia, some B-cell non-Hodgkin's lymphomas, and HL (16)(17)(18)(19)(20)(21)(22)(23)(24)35). Unmodified murine anti-CD25 was evaluated in a trial involving patients with ATL, a malignancy of mature CD4 + CD25 + immunosuppressing T lymphocytes (17,34).…”

“…Radioimmunotherapy using 90 Y-anti-ferritin and 131 I-anti-CD30 antibodies has resulted in partial (PRs) and CRs in HL (12-15). Deficiencies with these approaches reflect the lack of tumor specificity of ferritin-targeted antibodies and the small number of CD30-expressing Reed-Sternberg cells in the tumor.As an alternative, we identified CD25, the IL-2 receptor alpha subunit (IL-2Rα), as a more favorable target for systemic radioimmunotherapy of HL (16)(17)(18)(19)(20)(21)(22). The scientific rationale is that, with the exception of Treg cells, CD25 is not expressed by normal resting lymphoid cells, but it is expressed on both a minority of Reed-Sternberg cells and, critically, on T cells rosetting around Reed-Sternberg cells in HL (6,23,24).…”