Search PubMed⌕ Search

Biomedical subjects

T Tada

Publications and source records attributed to T Tada.

At least 433 records · Page 24Linked to original sources

Specific enrichment of the suppressor T cell bearing I-J determinants: parallel functional and serological characterizations.

A simple procedure to enrich the antigen (keyhole limpet hemocyanin, KLH)-specific suppressor T cell was described. The suppressor T cell from KLH)-immunized mice specifically bound to the KLH-coated Sephadex G-200 column at 37 degrees C, and was eluted from the column by cold (0-4 degrees C) medium. The helper T cell did not bind to the column under the identical condition. The suppressor T cell thus obtained had 100 times as potent suppressor activity as the original spleen cells in in vivo and in vitro secondary antibody responses against a hapten coupled to KLH. This procedure also enriched the cells bearing I-J determinants and Lyt-2,3 alloantigens, allowing us to study the phenotypic expressions on the suppressor T cell by direct serological procedures as well as by the use of the fluorescence activated cell sorter. Parallel functional and serological analyses indicated that the antigen-specific suppressor T cell belongs to a population of I-J+, Lyt-2+,3+ and Fc R- T cells.

Animals↗

Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex.

The locus of the gene that codes for the antigen-specific suppressive T-cell factor was determined to be in a new subregion "I-J" which locates between I-B and I-C subregions in the H-2 histocompatibility complex. This was shown by two different lines of evidence: (a) The absorbing capacity for the suppressive T-cell factor of several alloantisera against restricted I subregions did not correlate with their specificity for previously known Ia molecules which are coded for by genes in I-A and I-C subregions, but was associated with the specificity for the products of genes putatively present between I-B and I-C subregions. By the occurrence of special recombinant strains, i.e. B10.A(5R), B10.A(3R), B10.S(9R), and B10.HTT, which differ with respect to the I-J subregion, we were able to produce alloantisera which distinguish I-J subregion gene products. The absorption studies using these special alloantisera directed to I-J subregion clearly indicated that the suppressive T-cell factor is a product of I-J subregion gene(s), and that the molecule is distinct from known Ia molecules expressed on splenic B cells. (b) Taking advantage of the fact that there is a strict histocompatibility requirement for the effective suppression between the donor and recipient strains of the suppressive T-cell factor, we were able to determine the required identities of the genes in the H-2 complex existing among those present between I-B and I-C. Again, utilizing the T-cell factors obtained from special recombinant strains, i.e. B10.A(4R) and B10.A(5R), we were able to locate the gene that codes for the suppressive T-cell factor reactive only with relevant haplotype strains between I-B and I-C subregions. These results are most reasonably explained by the presence of a new subregion I-J which is specialized in coding for the suppressive T-cell factor as a different molecule from previously known Ia molecules.

Animals↗

Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. III. Dual gene control of the T-cell-mediated suppression of the antibody response.

The antigen-specific suppressive T-cell factor of mice, which had previously been shown to be an I region gene product, could effectively suppress the in vitro secondary antibody response of spleen cells from syngeneic or H-2 compatible mouse strains but not that of H-2 incompatible strains. The identities among genes in the left side half (K, I-A, and I-B) of the H-2 complex between the donor and recipient strains were found to be both necessary and sufficient for the induction of suppression. This suggests that the acceptor site for the suppressive T-cell factor is also determined by the gene present in the left side half of the H-2 complex. The cell type which expresses the acceptor site was found to be a subset of T cell. In general, the suppressive T-cell factor obtained from F1 mice could suppress the responses of both parental strains, and the parental factors could suppress the response of F1 mice. The results indicate that both suppressor and acceptor molecules are codominantly expressed on F1 T cells. There were found two types of defects in the expression of suppressor and acceptor molecules among mouse strains: A/J mice could not produce the suppressive T-cell factor despite that they could accept the factor produced by other H-2 compatible mouse strains. In contrast, all the B10 congeneic lines could produce the T-cell factor, but could not accept the factor produced by syngeneic and H-2 compatible non-B10 congeneic lines. The F1 hybrid of A/J and B10. A could both produce and accept the T-cell factor, and thus the expressions of suppressor and acceptor molecules were found to be dominant traits. These results indicate that the antigen-specific T-cell-mediated suppression is regulated by at least two genes both present in the H-2 complex, and that the complementation of these two genes is required for the induction of suppression.

Animals↗

The role of receptors for T cell products in antibody formation.

Immunocompetent cell interactions are achieved via direct contact between functionally different cell types or via interactions between soluble factors elaborated by regulatory T cells and specific receptors on responding cells for the T cell factors. In either case, there exist certain restrictions with respect to the effective interactions, which depend on the state of differentiation and genetic background of the responding cell type. Such restrictions are considered to be mainly determined by the development and nature of the receptor site on responding cell types for different T cell factors, which is now refered to the "acceptor" for the T cell factors. The presence of such acceptor sites on different populations of both T and B cells has been demonstrated in various experimental systems, and they are now considered to be the site by which responding cells receive appropriate signal for destination of their further differentiation. We have tried to review the nature and possible role of acceptor sites on both B and T cells for different T cell factors with respect to the induction and regulation of immune responses. A special emphasis was put on the genetic nature of the acceptor site. The observed genetic restrictions in the acceptance of T cell factors by responding cells suggest that such restrictions are needed for meaningful and unmistakable communications between funcionally different immunocometent cells. Furthermore, the presence or absence of acceptor sites for certain T cell factors is supposed to be a very important factor for determination of the immune responsiveness of animals against certain antigens, and thus in some cases the Ir gene effect may predominantly affect the expression of acceptor site. Possible implications of acceptor site in the regulation of antibody response and in the network of immunocompetent cell interactions are discussed.

Animals↗

Properties of antigen-specific suppressive T cell factor in the regulation of antibody response of the mouse. II. In vitro activity and evidence for the I region gene product.

An antigen-specific suppressive T cell factor, which was extracted from carrier-primed T cells, was further characterized in an in vitro secondary antibody response. The factor was capable of suppressing secondary IgG antibody response of primed spleen cells when it was added to the culture together with relevant antigen. The suppressive T cell factor was not released from primed T cells by a short-term culture with antigen, but was kept bound to the membrane of the residual cultured cells, only the physical disruption of which can release the T cell factor. The target of the suppressive T cell factor was determined as being the helper T cell, since the factor did not exert any effect in the absence of the helper T cell with identical specificity to that of the factor. The suppressive activity was completely absorbed with alloantisera specific for products of the I region of H-2 complex, although various anti-immunoglobulin antisera failed to do so. Close analysis of the specificity of alloantisera capable of absorbing the suppressor molecule indicated that the suppressive T cell factor may, in fact, be an I region gene product probably coded for by genes in I-A and/or I-B (including I-E) subregions.

Absorption↗

Properties of antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. I. In vivo activity and immunochemical characterization.

An antigen-specific suppressive T-cell factor was extracted from physically disrupted thymocytes and spleen cells of mice that had been immunized with soluble protein antigens. The factor, when inoculated into syngeneic normal mice, could induce a significant suppression of IgG antibody response against a hapten coupled to the carrier protein by which the donor of the suppressor factor was immunized. The suppressor factor was found only effective in suppressing the antibody response of syngeneic or H-2 histocompatible recipients. The suppressive T-cell factor was removed by absorption with immunoadsorbent composed of the relevant antigen, but not with any of those of anti-immunoglobulin antibodies. The factor was successfully removed by alloantibodies with specificity for the K end (H-2K, I-A and I-B) of the H-2 complex of the donor strain, but not by those for the D end (I-C, SsSlp, and H-2D). The activity was removed by absorption with a heterologous antithymocyte serum. The mol wt of the suppression T-cell factor was between 35,000 and 60,000 as determined by Sephadex G-200 gel filtration. The suppressive T-cell factor was found to be a heat-liable protein.

Animals↗

Half-lives of two types of rat homocytotropic antibodies in circulation and in the skin.

The half-lives of two classes of rat immunoglobulins with homocytotropic properties, i.e., IgE and IgG2a, in the circulating blood and in the skin were studied. The catabolism of both normal (reaginic) and pathological (myeloma) IgE proteins in circulation was found to be extremely rapid with a half-life of 12 h. In contrast, the half-life of IgE antibody in the homologous skin was calculated to be 7.4 days. On the other hand, the half-life of IgG2a in circulation was about 5 days regardless of normal or pathological origin. IgG2a protein was, however, rapidly cleared from the injected skin site with a half life of 2.4 days, a value not longer than that obtained with nonskin-sensitizing goat IgG. The results indicate that rat IgE has an extremely short half-life in circulation despite of its sensitization period in tissues, and that the affinity for the target cells, as well as the mode of sensitization, of the two classes of homocytotropic antibodies, IgE and IgG2a, is different.

Animals↗