concanavalin-a and Leukemia-Lymphoma--Adult-T-Cell

Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disorder caused by human T lymphotropic virus type 1 (HTLV-I). Although ATLL cells display an activated helper/inducer T-cell phenotype, CD4+ and CD25+, they are known to exhibit strong immunosuppressive activity. As regulatory T cells (Treg cells) express CD4+ and CD25+ molecules and possess potent immune response suppressive activity, we investigated a possible link between ATLL cells and Treg cells. In primary ATLL cells, the expression levels of the Treg cell marker molecules Foxp3 and glucocorticoid-induced tumor necrosis factor receptor family related protein (GITR) were significantly higher than in those from healthy adults. Furthermore, ATLL cells are unresponsive in vitro to concanavalin A stimulation and suppress the proliferation of normal T cells. GITR mRNA expression was induced by the HTLV-I transactivator Tax, and GITR promoter analyses revealed that this induction depends on the kappaB site from -431 bp to -444 bp upstream of the putative transcription site. Taken together, ATLL cells may originate from HTLV-I-infected Treg cells, and GITR seems to be involved in the progression to ATLL.

Topics: Adult; Cell Division; Cell Line, Tumor; Concanavalin A; DNA-Binding Proteins; Forkhead Transcription Factors; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Viral; Gene Products, tax; Glucocorticoid-Induced TNFR-Related Protein; Humans; Leukemia-Lymphoma, Adult T-Cell; Lymphocyte Activation; Receptors, Nerve Growth Factor; Receptors, Tumor Necrosis Factor; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes

We have carried out in vitro studies of hyperthermic effects on the viability, blastogenesis, and ultrastructural changes of atypical lymphocytes isolated from the peripheral blood of three patients with malignant lymphoma/leukemia. One was lymphocytic lymphoma/leukemia (T-cell origin), and the others were adult T-cell lymphoma/leukemia (both acute and smoldering type). In the cases of adult T-cell lymphoma/leukemia, the peripheral lymphocytes were found to be more sensitive to hyperthermia than those of non-ATL patients in terms of trypan-blue exclusion ability and blastogenesis ability with concanavalin A challenge. When heated under sublethal conditions, lymphocytes of both ATL and non-ATL patients exhibited the following characteristics: production of multilayered nuclear membranes, increase in vesicles (lysosomes), swelling of mitochondria, and cytoplasmic vacuolization.

Topics: Adult; Cell Differentiation; Cell Survival; Concanavalin A; Hot Temperature; Humans; Leukemia-Lymphoma, Adult T-Cell; Lymphocytes; Male; Microscopy, Electron; Middle Aged