PubMed Health⌕ Search

Biomedical subjects

M Tsudo

Publications and source records attributed to M Tsudo.

62 records · Page 4Linked to original sources
PubMed1985

Adult T leukemia cells produce a lymphokine that augments interleukin 2 receptor expression.

Human T-cell leukemia virus (HTLV)-infected cell lines derived from adult T-cell leukemia (ATL) express constitutively the receptor for Interleukin-2 (IL-2-R) and the associated antigen (Tac antigen). In contrast, the same antigen is transiently expressed by normal T-cells only after immune stimulation. Recently, it was reported that the constitutively expressed Tac antigen on ATL cells and cell lines was not down-regulated or modulated by anti-Tac antibody. Since the antigen was modulated on normal mitogen- or alloantigen-stimulated T-cells, we postulated that the regulation of IL-2-R may be abnormal on ATL cells; the synthesis of IL-2-R is continuously stimulated in these cells. A unique HTLV/ATLV(-) cell line (YT) derived from a child with acute lymphoblastic leukemia was found to express low levels of Tac antigen that could be enhanced by various stimuli, including conditioned medium (CM) derived from normal lymphocytes, but not by lectins (PHA, Con A). Of particular interest, the exposure of YT cells to CM from ATL cell lines with helper phenotype revealed the presence of factor(s) (ATL-derived factor, ADF) that augmented the synthesis and expression of IL-2-R/Tac antigen on YT cells and promoted YT cell growth. CM from HTLV(-) leukemia cell lines lacked both IL-2-R augmenting activity and a growth promoting activity. Immunoaffinity-purified IL-2 and recombinant gamma interferon also lacked IL-2-R augmenting activity. Moreover, the physicochemical analysis with Fast protein liquid chromatography (FPLC) revealed that ADF was quite different in pI point from the IL-2-R augmenting activity in CM from normal lymphocytes. These results suggested that ADF is a unique product of HTLV(+) cells. The possible relationship between ADF production, HTLV infection, and the abnormal expression of IL-2-R is suggested, and these abnormalities may be advantageous for the leukemogenesis and abnormal growth of ATL.

Adolescent↗
PubMed1984

Expression of Tac antigen on activated normal human B cells.

Two-color fluorescence analysis revealed that Tac antigen, which was previously reported to be restricted to T cells, was expressed on a proportion of normal B cells activated by Staphylococcus aureus Cowan I (SAC). Immunoaffinity-purified interleukin 2 (IL-2) induced the proliferation of SAC-activated B cells, and the proliferation was completely inhibited by anti-Tac antibody, which blocked the membrane binding and action of IL-2. These results suggest that an IL-2 receptor system is directly involved in the B cell immune response.

Antibodies, Monoclonal↗
PubMed1984

Abnormal expression of interleukin-2 receptor (Tac antigen) in adult T-cell leukemia.

Human T-cell leukemia/lymphoma virus type I(HTLV-I) infection appears to be closely associated with the leukemogenesis of adult T-cell leukemia (ATL), although its mechanism remains unclear. Since our previous report that leukemic cells from patients with ATL expressed Tac antigen (Ag) (interleukin-2 (IL-2) receptor) on their cell surface, we have been studying IL-2 receptors on ATL leukemic cells to see whether they are different from normal IL-2 receptors and whether they play a role in the neoplastic growth of ATL cells. Peripheral blood leukemic cells from 35 patients with ATL expressed IL-2 receptors which were detected by anti-Tac monoclonal antibody when examined immediately after the separation of cells or after culture for 24 or 48 hr. The number of anti-Tac binding sites ranged from 4,300 to 11,400 in fresh cells and from 6,100 to 96,000/cell in short term cultured leukemic cells, whereas phytohemagglutinin-P(PHA-P)-stimulated normal T cells exhibited 7,000 to 35,000 anti-Tac binding sites/cell. HTLV-I-infected cell lines such as MT-1 and HUT-102 expressed a markedly enhanced number of Tac Ag molecules. Leukemic cells from 15 ATL patients showed no or very poor proliferative response to various concentrations of IL-2, although they expressed Tac Ag. Radiolabeled IL-2 binding experiments revealed that ATL leukemic cells could bind IL-2 although the number of IL-2 binding sites was much less than that of anti-Tac binding sites. IL-2 receptors on ATL cells, unlike normal activated T cells, were not modulated (down-regulated) by anti-Tac antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Surface↗
PubMed1983

Cell surface phenotype and in vitro function of adult T-cell leukemia cells.

The cell surface phenotypes of leukemic cells obtained from 30 patients with adult T-cell leukemia (ATL) were examined by means of a panel of OKT monoclonal antibodies and an anti-Tac monoclonal antibody. These leukemic cells were reactive with OKT1, OKT3, OKT4, OKT10, and OKT11 but not with OKT5, OKT6, OKT8 antibodies, suggesting that they were derived from peripheral mature cells included in the OKT4+ "helper/inducer" T-cell subset. Functionally, leukemic cells from none of the nine patients studied stimulated pokeweed mitogen (PWM)-driven immunoglobulin (Ig) synthesis by normal B cells. Suppressor cell activity, however, was found in 17 of 25 patients in PWM-induced Ig production. Fresh or cultured ATL cells from 22 of 23 patients tested expressed Tac antigen (interleukin-2 receptor) on the cell surface. The significance of Tac antigen on ATL cells is discussed in relation to the abnormal regulation of Tac antigen and leukemogenesis.

Adult↗
PubMed1983

Failure of regulation of Tac antigen/TCGF receptor on adult T-cell leukemia cells by anti-Tac monoclonal antibody.

Anti-Tac monoclonal antibody, which blocks the membrane binding and action of human T-cell growth factor (TCGF), is strongly proposed to recognize TCGF receptor. We have demonstrated that anti-Tac antibody reacted with leukemic cells from patients with adult T-cell leukemia (ATL) and reacted with T-cell lines established from ATL cells. Although antigenic modulation, or down-regulation, of Tac antigen on activated normal T cells was induced by anti-Tac antibody, the expression of Tac antigen on ATL cells or T-cell lines was not affected when examined by the fluorescence-activated cell sorter (FACS) and the radioassay using 125I-staphylococcal protein A. These results indicate that regulation of Tac antigen-TCGF receptor is different between normal and malignant T cells, suggesting that failure of down-regulation of Tac antigen on leukemic cells by anti-Tac antibody may play an important role in the malignant proliferation of ATL cells.

Animals↗
PubMed1982

Modulation of Tac antigen on activated human T cells by anti-Tac monoclonal antibody.

A monoclonal antibody termed anti-Tac antibody is reactive with activated and functionally mature human T cells, but not reactive with resting T cells or B cells. We found that the expression of Tac antigen on activated T cells was inhibited by the addition of anti-Tac antibody in the culture of T cells activated with Con A or alloantigen. In the mixed lymphocyte culture, the expression of Ia-like antigen on allo-activated T cells was also inhibited by anti-Tac antibody, although the antibody does not recognize Ia-like antigen. However, anti-Ia monoclonal antibody did not suppress the expression of either Tac or Ia-like antigen. In addition, Tac antigen expressed on activated T cells was modulated by anti-Tac antibody cultured with activated T cells at 37 degrees C for 48 hr. Antigenic modulation, which means a specific loss of Tac antigen from the cell surface of T cells, was detected by the indirect immunofluorescence method. Tac antigen was reexpressed on T cells after restimulation when the anti-Tac antibody was removed, whereas Ia-like antigen already expressed on allo-activated T cells was not modulated by anti-Tac antibody. These results suggest that Tac and Ia-like antigens are carried on different molecules, both of which are closely linked in expression on activated T cells. The expression of Tac antigen may be essential for the following expression of Ia-like antigen.

Antibodies, Monoclonal↗