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Y Dohi

Publications and source records attributed to Y Dohi.

9 recordsLinked to original sources

Antigen- and receptor-driven regulatory mechanisms. I. Induction of suppressor T cells with anti-idiotypic antibodies.

Delayed-type hypersensitivity (DTH) to the azobenzenearsonate (ABA) hapten can be readily induced in A/J mice injecting ABA-coupled syngeneic spleen cells subcutaneously. To further characterize this T-cell-dependent immunological phenomenon, the effect of passively administered anti-cross-reactive idiotype common to anti-ABA antibodies of A/J mice (CRI) antibodies on the development of ABA-specific DTH was investigated. Animals given daily injections (of minute amounts) of anti-CRI antibodies subsequent to immunization with ABA-coupled cells show significant reduction of ABA specific responses. This inhibition is antigen specific and requires the intact immunoglobulin molecule, as F(ab')2 treatments were ineffective in suppressing the reaction. Investigations of the mechanism of the anti-CRI-induced suppression of ABA DTH revealed that the observed suppression is a result of the activation of suppressor cells. Spleen cells taken from animals which received anti-CRI antibodies were able to adoptively transfer suppression to naive recipients. This suppression was shown to be mediated by T cells, as anti-Thy1.2 plus complement completely abrogated the transfer of suppression. In addition, animals pretreated with low doses of cyclophosphamide were not suppressed by the administration of anti-CRI antibodies. The genetic restriction of anti-CRI-induced suppression was demonstrated. Antibodies to the major cross-reactive idiotype, (CRI) associated with anti-ABA antibodies in A/J mice were unable to suppress the development of DTH to ABA in BALB/c mice (H-2d, Igh-1a). Such antibodies were, however, fully active in suppressing ABA DTH in the allotype-congenic C.AL-20 strain which has an allotype (Igh-1d) similar to that of A/J (Igh-1e) on a BALB/c background, and which produces humoral antibodies with the CRI.

Animals

Suppression of idiotype and generation of suppressor T cells with idiotype-conjugated thymocytes.

Inoculation of A/J mice with syngeneic thymocytes conjugated with specifically purified A/J anti-phenylarsonate (anti-Ar) antibodies, selectively suppressed the subsequent synthesis of those anti-Ar antibodies which carry the major cross-reactive idiotype. High titers of anti-Ar antibodies were produced upon subsequent immunization but in most mice the idiotype was undetectable. Suppression similarly occurred in F1(A/J X BALB/c) and in C.AL-20 mice. Although some mice were suppressed when unconjugated antibody was injected, the suppressive effect was much more pronounced, particularly in the F1 and C.AL-20 recipients, when the antibody was coupled to thymocytes. The state of suppression could be adoptively transferred with T cells to mildly irradiated syngeneic recipients. A population enriched for B cells had little if any suppressive effect. There was no requirement for antigen in the generation of suppressors. Thymocytes conjugated with antibody did not induce idiotype-specific suppression in mice that had been recently challenged with antigen. Thymocytes from BALB/c and C57BL/10 mice were effective carriers for the anti-Ar antibodies, i.e., there was no evidence for H-2 restriction. The experiments demonstrate the feasibility of suppressing idiotype production and generating idiotype-specific suppressor T cells without the use of anti-idiotypic antibody or antigen.

Animals

Immunological unresponsiveness in mice. II. Cellular basis of immunological unresponsiveness induced in foetal and neonatal mice by transfer of human gamma-globulin by the maternal route.

The cellular basis of the mechanism of immunological tolerance to human gamma-globulin (H gamma G) induced in foetal and neonatal mice by materno-foetal or materno-neonatal transfer after a single injection of tolerogen (deaggregated H gamma G) into the mothers was investigated using a cell transfer system and assays of passive haemagglutinating antibodies and plaque-forming cells to H gamma G. The results demonstrated that B cells are mainly involved in the tolerance induced on the fourteenth day of gestation, whereas inactivation of T cells may account for the tolerance induced on the eighteenth day of gestation and in the neonatal stage. Treatment of the mothers with tolerogen and then anti-H gamma G serum reduced the tolerance induced on the fourteenth day of gestation, but did not affect that induced on the eighteenth day of gestation and in the neonatal stage. Cell transfer experiments showed that B-cell tolerance induced on the fourteenth day of gestation was prevented by passive antibody, while T-cell tolerance induced on the eighteenth day of gestation and in the neonatal stage was not affected by passive antibody. Assay of the anti-DNP antibody response after immunization with DNP10-H gamma G showed that treatment of mice with the tolerogen on the eighteenth day of gestation, but not the fourteenth day of gestation, inactivated H gamma G-reactive helper cells. The significance of these results is discussed in relation to the results of the cell transfer experiments described as above.

Animals

Antigenic structures of Salmonella flagella. I. Presence of an antigenic determinant exposed at one end of flagellar fragments.

Salmonella flagellin, which is a constitutional subunit of the flagellum, was shown to have antigenic determinants distinct from its own serotypic ones. These antigenic determinants were found to be common to flagellins from the so-called g-complex serotypes, such as fg, mt, gm, gt, gp and gmptu, but not to those from other serotypes, such as a, i or enx. Rabbits immunized with flagellin of serotype "fg" produced anti-"fg" flagellin antibodies. Only about 20 percent of these corresponded to the serotype determinants of the "fg" on the surface of the flagella, and the remaining 80 percent reacted with the flagellin of the unrelated serotype "mt", and corresponded to the distinct determinants common to the flagellin molecules. These antigenic determinants were detected by the immunoferritin technique at only one, not both, terminals of the flagellar fragments, suggesting that a unidirectional arrangement of flagellin subunits in the flagella may expose the inherent conformation of the subunits at only one end of the flagellum.

Antibodies, Bacterial

Comparative studies on antibody formation against hen egg white lysozyme and its split fragment.

A peptide fragment Fr. 17 (Lys1-Cys-Asn27 Leu129-Cys-Ala122) of hen egg white lysozyme (HL) was previously found to retain at least one antigenic determinant region of the native protein. In this work a highly purified preparation of Fr. 17, contaminated with less than 0.01% HL and less than 1% of other fragments was found to be strongly immunogenic to rabbits. The kinetic patterns of antibody formation against Fr.17, assayed by passive hemagglutination (PHA), were quite different from those of antibody formation against HL. The specificity of the antibody elicited to Fr. 17 was mainly directed to the Fr. 9-10-a region (Ala11-Asn27) while that of the antibody elicited to the Fr. 17 region in native HL was directed to the Fr. 15-b region (Lys1-Cys-Ala10 Leu129-Cys-Trp123). It is concluded that in the process of antibody formation, the recognition of the Fr. 17 region in native HL is different from that of fragment Fr. 17.

Animals