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H Ramseier

Publications and source records attributed to H Ramseier.

At least 37 records · Page 2Linked to original sources

Transplantation tolerance at the T-lymphocyte receptor level. II. Interaction of T-cell receptors with alloantigen and with anti-receptor antiserum.

CBA T lymphocytes deprived temporarily of receptors for alloantigens A[RS(A)] cultivated in vitro for 30 h with anti-receptor antibody-forming (AxCBA)F1 spleen cells were capable of resynthesizing RS(A) if primed F1 cells exceeded parental T cells by a factor of 25 or less, but not if the excess was 50-fold or more. This indicated that resynthesis of CBA T-cell RS(A) was successful if primed F1 cells formed insufficient amounts of anti-CBA T-cell RS(A) antibody. Abortive or successful receptor resynthesis was measured by two parameters, (a) reappearing RS(A) formed PAR together with A alloantigens of (AxCBA)F1 spleen cells and (b) budding receptors bound anti-receptor antibody. CBA B lymphocutes did not interfere with these reactions. A search for putative T suppressor cells in the F1 cell population was unsuccessful. PAR formation and anti--RS antibody consumption by reappearing receptors differed temporally: receptors forming PAR were present after a delay lasting 8 h; receptor structures fixed anti-RS antibody as early as 5 h after being cultivated. With due caution, these results might reflect processes operating in maintenance of transplantation tolerance, suggesting that this condition is a serum-mediated suppression of long duration. The suppression would encompass continued neutralisation of receptors for the alloantigen to be tolerated by anti-T-cell receptor antibody formed by the F1 chimeric cells within an animal with acquired transplantation tolerance.

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Generation of cytolytic T lymphocytes in vitro. VIII. failure of anti-RS antisera to inhibit the generation of cytolytic T lymphocytes or cytolytic T lymphocyte activity.

Antibody reactive with "recognition structures" (RS) of mouse lymphoid cells for alloantigens (anti-RS) was prepared by immunization of F1 hybrid mice with parentalstrain lymphoid cells or with antibody produced in one parental strain against alloantigens of the other parental strain. Such antisera prevented generation of the "product of antigenic recognition" (PAR) that is produced within a few hours in cultures prepared with a mixture of lymphoid cells from genetically disparate mice. However, treatment of responding lymphoid cells with anti-RS sera and complement did not inhibit generation of cytolytic T lymphocytes (CTL) in mixed lymphocyte cultures (MLC). Treatment of cells obtained from MLC with anti-RS sera and complement failed to inhibit cytolytic activity of such cells for specific alloantigens.

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Spontaneous release of T cell receptors for alloantigens. II. Induction of antibodies to T cell receptors.

Spleen cells from normal mice, when cultivated in vitro, released receptors or recognition structures (RS) for alloantigens into the surrounding medium. The spontaneous shedding of receptors was revealed by their ability to induce the formation of anti-recognition structure(anti-RS) antibodies upon injection into appropriate F1 hybrid recipients. Cell suspensions containing T and B lymphocytes and those containing T lymphocytes were capable of inducing anti-RS antibody formation, whereas suspensions devoid of T cells were incapable of doing so. Receptors shed from such cell suspensions during a 24-hour cultivation period gave exactly the same results. Cell-free culture supernatants, however, incited higher anti-RS antibody titers, presumably because of an accumulation of RS. The capacity of released T cell receptors to recognize alloantigens as determined in the PAR assay and their ability to induce anti-RS antibodies went roughly parallel.

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Spontaneous release of T cell receptors for alloantigens. III. The effects of anti-T cell receptor antiserum, of alloantiserum and of trypsin on T cell receptor release.

Spleen and lymph node T lymphocytes cultivated in vitro spontaneously released receptors for alloantigens. Among the various specificities, those receptors fitting certain alloantigens could be absorbed by formolized cells or proper genotype without influencing receptors for other alloantigens. Shedding of T cell receptors could be inhibited for 8 h by treating cells with antisera directed against T cell receptors (anti-RS antisera). Inhibition experiments indicated that resynthesis of T cell receptors appears to be complete by 8 h. Experiments on prevention of receptor shedding revealed highly specific and presumably cytotoxic elimination of T cells with receptors for given alloantigens. Treatment of cells with alloantiserum obtained by skin graft rejection failed to inhibit spontaneous release of T cell receptors, whereas treatment of lymphocytes with trypsin resulted in an 8-h delay of receptor shedding similar to that after treatment of cells with anti-RS antisera. This inhibition was, however, nonspecific.

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Idiotype positive T cells visualized by autoradiography and electron microscopy.

Anti-idiotypic antibodies were prepared in (CBA X C57BL/6)F1 hybrid mice by immunization either with CBA anti-C57BL/6 alloantiserum or with purified CBA thymus-processed lymphoid cells (T cells) Iodinated anti-mouse Ig or triple sandwich ferritin-labeling techniques served to visualize the reaction between idiotype and anti-idiotype. From 5 to 10% of purified CBA T cells appeared to carry receptors for C57BL/6 antigens. Heavily labeled cells had the morphology of small lymphocytes.

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Spontaneous release of T-cell receptors for alloantigens. I. Recognition of alloantigens and receptor release dynamics.

In vitro cultivation of murine spleen cells resulted in a spontaneous release of receptors for alloantigens. This was revealed by the capacity of cell-free culture supernates to recognize alloantigens as measured in the PAR assay. Qualitatively, recognition responses obtained with these supernates reproduced faithfully those found with the corresponding cells. Large amounts of receptors were released by untreated spleen cells and by spleen cells treated with a rabbit antimouse immunoglobulin serum and complement, smaller amounts were released by bone marrow cells, and native thymus cells released none. Spleen cells from nude mice and spleen cells from normal mice treated with anti-theta serum and complement showed no release of receptors. It was concluded that receptors active in the PAR test were of T-cell origin. Release of T-cell receptors was found to be discontinuous and proceeded in waves. The amount of released receptors depended on the number of cells cultivated. Release occurred at 37 degrees C but not at 4 degrees C. Interaction with antigen, however, was temperature-independent. In contrast to T-cell receptors, a release of H-2 antigens could not be detected with the culture conditions employed.

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Cellular receptors. effect of anti-alloantiserum on the recognition of transplantation antigens.

The possibility that a rat alloantiserum DA anti-Lewis possesses similar recognition structures for Lewis transplantation antigens, as do DA immunocompetent cells, was investigated by raising an antiserum against this alloantiserum in (Lewis x DA)F(1) hosts. This antiserum, as well as one provoked by injecting DA lymphoid cells, was active against recognition structures for Lewis antigens of DA immunocompetent cells. The anti-(DA anti-Lewis) antiserum displayed the same degree of specificity as was found previously for anti-recognition structure sera prepared by injecting parental strain lymphoid cells into F(1) hosts. Since the activities of antisera raised against cell-bound receptors or against the antigen-binding region of an immunoglobulin were indistinguishable, it was concluded that the functional part of cell-associated receptors might be structurally similar to the variable portion of an immunoglobulin.

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