4-Hydroxy-3-nitro-phenylacetyl (NP)-specific T cell hybridomas.
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Biomedical subjects
Publications and source records attributed to T Takemori.
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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.
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.
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.
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.
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Passively transferred thymocytes and spleen cells from donors primed with keyhole limpet hemocyanin (KLH) exerted differential suppressive effect on IgM and IgG antibody responses of syngeneic recipients immunized with DNP-KLH depending primarily on the time when KLH-primed cells were transferred. This was demonstrated by the decrease in the numbers of DNP-specific direct and indirect PFC in the spleen of the recipients given KLH-primed cells at different times during primary and secondary immunization. Whereas the cell transfer simultaneously with or 2 days after the primary immunization produced only slight suppression of the peak IgM antibody response, it caused profound suppression of late IgM and IgG antibody responses. By contrast, the cell transfer 3 days after the immunization produced immediate suppression of the ongoing IgM antibody response resulting in its earlier termination, while being unable to prevent the induction of IgG antibody response. KLH-primed cells could moderately suppress the secondary anti-DNP antibody response, in which IgG antibody response was found to be slightly more sensitive than IgM antibody response to the suppressive influence of KLH-primed cells. The suppressive effect of the KLH-primed spleen cells was completely eliminated by the in vitro treatment of the cells with anti-theta and C before cell transfer, indicating that cells responsible for the suppression are, in fact, T cells. The suppression of DNP-specific antibody response by KLH-primed T cells was achieved only if the recipients were immunized with DNP-KLH but not with DNP-heterologous carrier, suggesting that direct interaction between T and B cells is necessary for the suppression of the antibody response. It is concluded that susceptibility of B cells to the specific suppressive influence of T cells is inherently different depending on the differentiation stage of B cells and on the immunoglobulin class they are destined to produce.
Passive transfer of thymocytes and spleen cells from donors primed with keyhole limpet hemocyanin (KLH) caused significant decrease in the average avidity of anti-DNP antibodies produced by direct and indirect PFC in the recipients in both primary and adoptive secondary antibody responses against DNP-KLH. The analysis of the avidity distribution of antibodies produced by plaque-forming cells (PFC) indicated that the observed decrease in the average avidity is primarily due to the selective loss of high avidity subpopulation of PFC leaving low avidity subpopulation relatively unaffected. The degree of suppression in antibody avidity did not correlate with the reduction in the number of PFC, and thus causing the "shift" of avidity distribution of PFC to the low avidity end. These results indicate that the "maturation" of antibody in the T-cell-dependent antibody response is influenced by the carrier-specific suppressor T cells with respect to the emergence and selection of B cells having high affinity receptors for hapten. It is suggested that B cells binding antigen with high affinity receptors would be more easily affected than those with low affinity receptors by specific suppressor T cells which are capable of reacting the carrier portion of the same antigen.
Immunogenicity of culture filtrates of various air-born fungi with respect to reaginic antibody formation was tested in the rat. Animals immunized with two successive injections of culture filtrates of fungi with the aid of Bordetella pertussis vaccine as an adjuvant produced fairly high titers of reaginic antibodies of the IgE class. Little cross-reactivity was detected between reagins induced by different strains of fungi. The reaginic immunogenicity was only found in the culture fieltrate produced by the surface culture, in which large amounts of conidia were formed, but not in the filtrate obtained from the shaking culture, in which only mycelial components were growing. Therefore, it was suggested that allergens responsible for the reaginic antibody formation derive from the conidium but not from the mycelium. The results indicate that air-born fungi are potentially immunogenic for production of reaginic antibodies, and further suggest their causative roles in human atopic diseases.