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T Tada

Publications and source records attributed to T Tada.

At least 415 records · Page 23Linked to original sources

Functional and molecular organisation of an antigen-specific suppressor factor from a T-cell hybridoma.

Thymus-dependent (T) lymphocytes have been shown to have antigen specificity. The antigen receptor on T lymphocytes, in contrast to that on B lymphocytes, does not appear to be of the conventional immunoglobulin (Ig) type. Studies on the antigen-specific factors derived from helper and suppressor T cells (Ts) demonstrated that they possess determinants with antigen binding affinity and products of genes in the H-2 complex (MHC). Furthermore, antibodies against the variable region of Ig heavy chains or idiotypes have been shown to react with T-cell antigen receptors as well as antigen-specific helper and suppressor T-cell factors (TsF). It is, therefore, conceivable that at least two gene products are involved in the structural entity of these receptors: one each coded for by genes in either. To establish the molecular nature of the recognition component of T cells we have used homogeneous TsF from a T-cell hybridoma with a specific function. We report here that the antigen binding and I-J coded molecules on TsF are independently synthesised in the cytoplasm, and are secreted as an associated form of the two molecules; this association is required for antigen-specific suppression of antibody response.

Animals↗

A glycolipid on the surface of mouse natural killer cells.

Cytotoxic treatment with rabbit antiserum raised against purified glycosphingolipid "asialo GM1" was capable of eliminating natural killer (NK) activity of spleen cells from different inbred mouse strains including CBA/J, C57BL/6, BALB/c, AKR, and athymic nude mice. The anti-asialo GM1 antiserum showed little cross-reactivity with structurally related glycolipids, e.g. GM), GD 1 b and asialo GM2 in the microflocculation test. The specific reactivity of this antiserum with NK cells was confirmed by the quantitative absorption of anti-NK activity with graded amounts of asialo GM1 but not with other glycosphingolipids. The absorption of anti-brain-associated T cell antigen (anti-BAT) with asialo GM1 also effectively diminished its anti-NK activity, leaving the ability to kill T cells intact. This suggests that the antibody to asialo GM1 is responsible for the anti-NK activity contained in the anti-BAT antiserum. In contrast to the extreme sensitivity of NK cells to anti-asialo GM1, alloreactive cytotoxic T killer cells generated in the mixed lymphocyte culture were not killed by anti-asialo GM1 and complement. These results indicate that asialo GM1 is expressed on mouse NK cells in a high concentration.

Animals↗

Suppression of IgE antibody formation in mice with nonspecific stimulation.

Effects of administration of various adjuvants were examined for the induction of IgE antibody response against a hapten-carrier conjugate in the mouse. It was confirmed that alum was an excellent adjuvant for induction of IgE antibody response, while poly A:U, CFA and LPS had much less activity. However, when these adjuvants were administered before immunization with antigen and alum, they suppressed the forthcoming antibody response to various degrees. Even alum exerted a profound suppressive effect when it was given before immunization. Such suppressive effect of alum and poly A:U was partially overcome by incorporating in the adjuvant the carrier protein. In contrast the suppressive effect of CFA was overcome by incorporating in the CFA an unrelated carrier conjugated to the same hapten (DNP). The results indicate that the target of the adjuvants is different from one to the other and further give a clue to study the possible application for the suppression of IgE antibody formation.

Adjuvants, Immunologic↗

Analysis of cell surface antigen on neoplastic lymphocytes by the use of anti-human brain serum.

Cell surface antigens on neoplastic lymphoid cells of T cell lineage were analyzed with a fluorescence-activated cell sorter (FACS-II) by utilizing rabbit antisera raised against human brain tissue (anti-Br) and fetal thymocytes (anti-Ty). Both before and after extensive absorption with normal peripheral blood lymphocytes (PBL), the anti-Br antiserum was capable of staining neoplastic lymphoid cells from patients with Sézary syndrome, mycosis fungoides, thymoma, and chronic lymphocytic leukemia. The absorption of anti-Ty with normal PBL, however, resulted in loss of the ability to stain normal bone marrow cells and preabsorbed with normal PBL was found to stain normal bone marrow cells and neoplastic myeloid cells but not fetal thymocytes. It is suggested that the absorbed anti-Br is capable of detecting differentiation antigens present on immature hematopoietic cells in the bone marrow, which would be anomalously expressed on neoplastic lymphoid cells to T cell lineage.

Adolescent↗

Surface markers on natural killer cells of the mouse.

Rabbit antiserum against mouse brain tissue (anti-brain-associated T cell antigen, anti-BAT) was capable of killing splenic natural killer (NK) cells of CBA/J, BALB/c, C 57 Bl/6J, C 3 H/He and nude mice, which were detected with Molony virus-induced lymphoma (YAC-1) and radiation-induced leukemia (RL male 1) cells as targets. The same antiserum abolished T cell functions, e.g. carrier-specific helper function and the responsiveness to concanavalin A, but not B cell functions, e.g. immunological memory for the secondary antibody response and the responsiveness to lipopolysaccharide. After absorption of the anti-BAT with thymocytes, the ability to kill T cells was completely abrogated, leaving the activity to kill NK cells intact. No other heterologous and isologous antisera, i.e. rabbit anti-mouse thymocyte antiserum, goat antiserum against antigens shared by thymus and B cells, anti-Thy-1.2 and anti-Ia antisera, could eliminate NK function regardless of their definite reactivity against T or B cells. The results indicate that the absorbed anti-BAT can distinguish NK cells from other known subsets of T and B cells.

Animals↗

Immunological abnormalities of aging: an analysis of T lymphocyte subpopulations of Werner's syndrome.

Two T lymphocyte-specific antisera, i.e. naturally-occurring auto-antibody to T cells of systemic lupus erythematosus patients (natural T cell toxic autoantibody) and heterologous antiserum against human brain tissue (antibrain-associated T-cell antigen), were used to detect cell surface antigens of human peripheral T lymphocytes. Nylon column-purified T cells from normal aged individuals and patients with Werner's syndrome (a premature aging syndrome) were reacted with these auto- and heterologous antibodies followed by staining with appropriate fluorescence reagents. The cells were subjected to the automated analysis with fluorescence-activated cell sorter. Fluorescence profiles to T cells of both aged individuals of over 90 yr and Werner's syndrome showed a very similar pattern, with a drastic decrease in the population that had high fluorescence intensity stained with either antiserum accompanied by the relative increase in the cell population that had low fluorescence intensity. Natural T cell toxic autoantibody comparable to that detected in systemic lupus erythematosus patients was found in the serum of six out of seven patients with Werner's syndrome, whereas normal aged individuals produced no such an autoantibody. The results suggest that Werner's syndrome has a change in the lymphocyte population very similar to old individuals, and that such a change is caused by the production of autoantibodies reactive to T lymphocytes.

Adolescent↗

Differential activation of cytotoxic and suppressor T cells against syngeneic tumors in the mouse.

The cytotoxic T cell against a methylcholanthrene-induced sarcoma, S1509a, was induced in syngeneic mice by deliberate immunization with mitomycin C (MMC)-treated live tumor cells. The soluble tumor antigen (STA) extracted from the same tumor by 3 M KCl was, however, unable to induce the cytotoxic T cell upon immunization, although it was able to activate predominantly the suppressor T cell that then specifically suppressed the effect of the cytotoxic T cell against the homologous tumor. The suppressor T cell generated by STA had the same characteristics as those found in tumor-bearing animals: 1) The suppressor T cell has a very strict specificity against individual tumors; 2) The cell expresses cell surface determinants controlled by genes in the I-J subregion of the mouse H-2 complex. The activity of the cytotoxic T cell was completely inhibited by live tumor cells but not by STA, whereas that of the suppressor T cell was neutralized by STA. The results that cytotoxic and suppressor T cells are activated under different conditions, and that the antigenic determinants recognizable by these two cell types are not the same. The soluble extract contains only the determinants recognizable by the suppressor T cell, and the cytotoxic T cell can be activated only by the determinants associated with self antigen present on the surface of live tumor cells.

Animals↗

Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells.

We have described here two distinct types of carrier-specific helper T cells which act independently and synergistically to augment the B-cell response to a hapten. They are separable by passage through a nylon wool column. The first type of helper T cell, which we designate as Th1, is nylon nonadherent, and can help the response of hapten-primed B cells only if the haptenic and carrier determinants are present on a single molecule (cognate interaction). The second type of helper T cell, Th2, adheres to the nylon wool column, and can help the B-cell response to a hapten coupled to a heterologous carrier upon stimulation with unconjugated relevant carrier (polyclonal interaction). The addition of a small number of Th2 to the mixture of Th1 and B cells significantly augmented the net response to the hapten carrier conjugate. Both Th1 and Th2 cells belong to the Lyt-1+,2-,3- subclass. Th1 has no detectable Ia antigen, whereas Th2 is killed by certain anti-Ia antisera and complement. The Ia antigen detected on Th2 was found to be controlled by a locus in the I-J subregion. The results clearly established the fact that there are two distinct pathways in the T- and B-cell collaboration, which involves two different subsets of carrier-specific helper T cells.

Animals↗