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Biomedical subjects

C L Reinisch

Publications and source records attributed to C L Reinisch.

12 recordsLinked to original sources

Autoimmune vasculitis in MRL/Mp-lpr/lpr mice: orthochromatic basophils participate in the development of delayed-type hypersensitivity angiitis.

The pathogenesis of autoimmune vasculitis is poorly understood. Understanding the immunologic mechanisms governing this disease requires precise identification of the cells which comprise the lesion. In this report, we have evaluated tissue sections from MRL/lpr mice from 16 to 45 weeks of age, representing all stages of clinical vasculitis. We demonstrate that basophil myelocytes participate in the evolution of the delayed-type hypersensitivity (DTH) response which initiates and perpetuates autoimmune vasculitis in these mice. These findings raise questions regarding the immunologic mechanisms by which basophils develop in this lesion and the interaction of basophils. VSMCs and lymphocytes in vasculitic angiodestruction.

Animals

Regulation of cytotoxic T-cell reactivity to syngeneic tumors by the thymus.

Adult thymectomy has been shown to result in the enhanced capacity of splenic T cells to respond to and lyse syngeneic tumor cells in vitro. In addition, T cells from thymectomized mice which kill syngeneic tumor cells do not lyse either normal lymphoid or mitogen-stimulated syngeneic lymphoblast target cells. These findings indicate that the thymus exports a subpopulation of T cells sensitive to adult thymectomy which regulates the generation of cytolytic T cells directed against syngeneic tumor cells.

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Induction of immunoregulatory T cells by adjuvant.

The effect of adjuvant on the generation of suppressor cells in the thymus was investigated. C57Bl/6 mice were injected i.p. with complete Freund's adjuvant (CFA), and the capacity of thymocytes and splenic T cells to suppress the in vitro generation of cytolytic T cells was studied. Suppressor thymocytes were detected within two days after CFA inoculation and preceded the appearance of suppressor T cells in the spleen by six days. Characterization of the suppressor thymocyte populations showed that they inhibited primary but not memory T cell responses in vitro. We suggest that the initial step in the regulation of the primary immune response by adjuvant is the generation of suppressor cells in the thymus. Thymic suppressors subsequently migrate to peripheral lymphoid tissue where they inhibit cytotoxic, but no helper, T cell function.

Animals

Suppressor cell regulation of immune response to tumors: abrogation by adult thymectomy.

The regulatory role of the adult thymus on the appearance of cytotoxic and suppressor T cells (thymus-derived lymphocytes) to allogeneic and autochthonous virus-induced tumors in mice was investigated. It was demonstrated that C57BL/6 mice challenged with allogeneic P815 mastocytoma cells and complete Freund's adjuvant failed to develop cytotoxic cells but instead developed suppressor T cells which inhibited cytotoxic T cell function. Further, adjuvant-induced suppressor cells prevented the primary in vitro induction of cytotoxic T cells to P815 mastocytoma cells. In contrast, adult thymectomized animals, when challenged with adjuvant and allogeneic cells, had a normal cytotoxic response in vivo and their cells could not inhibit the generation of cytotoxic T cells in vitro. These studies suggested that the intact adult thymus was necessary for the induction of suppressor cells. Moreover, suppressor cells regulated cytotoxic T cell activity both in vivo and in vitro. Further, it was shown that adjuvant could prevent the normal immune response to virus-induced tumors. BALB/c mice treated with murine sarcoma virus developed tumors which reached a maximal size by day 14 and then regressed. Sham thymectomized animals treated with virus and complete Freund's adjuvant to generate suppressor cells died from progressive tumor growth. In contrast, thymectomized animals similarly treated had normal regression of tumor and survived. These studies lead to the conclusion that the adult thymus may regulate immune responsiveness by the export of suppressor T cells which regulate other T cell responses to both allogeneic and tumor antigens.

Animals

T and B lymphocyte migration into syngeneic tumors.

The migration of splenic T and B lymphocytes into syngeneic tumors undergoing immunologic rejection was investigates. Spleen cells were obtained from normal BALC/c mice or BALB/c mice bearing tumors induced by murine sarcoma virus (MSV). Either whole spleen cells or immunoabsorbent purified T and B cells were radiolabeled with sodium chromate-51 and injected i.v. into normal or MSV inducted-tumor bearing syngeneic recipients. Twenty-four hours later the recipient mice were sacrificed and radioactivity was assessed for tumor, contralateral normal muscle, the lymph nodes draining the tumor and contralateral draining lymph nodes, peripheral lymph nodes, spleen, and liver. Both T and B lymphocytes from either normal or MSV tumor-bearing animals show greatly increased migration into the tumor when compared with normal muscle. Migration of T cells from both normal and MSV tumor bearers was 30 times that of migration to normal muscle. B cells from tumor-bearing mice, on the other hand, localized in the tumor itself only 50% as frequently as did B cells from normal animals. In addition, T cells from MSV tumor bearers were found in the highest proportion in the lymph node draining the tumor site. We conclude that T and B lymphocytes from either normal or tumor-bearing mice migrate to a syngeneic tumor undergoing immunologic rejection. In contrast, the migration of both T and B cells from tumor-bearing animals was decreased to the peripheral lymph nodes at the time of maximum tumor growth.

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Potentiation of cytotoxic T-cell function by virus.

Inoculation of C57BL/6J mice with allogeneic P815 mastocytoma cells in the presence of simian virus 40 (SV40), a DNA tumor virus, led to an enhanced cytolytic T-cell response to P815 in vivo. Cytotoxic function was also augmented if SV40 was given subsequent to a primary immunization, even when mice were given a suboptimal dose of immunizing cells. Although SV40 increased the cell-mediated immune response to allogeneic cells, it did not enhance the antibody response to the soluble antigen dinitrophenyl bovine gamma-globulin, a helper T-cell-dependent response. Thus it appeared that SV40 had a selective adjuvant effect on lymphocyte subpopulations, since it increased cytotoxicity but not helper T-cell function.

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Adjuvant regulation of T cell function.

The effect of complete Freund's adjuvant (CFA) on distinct T cell functions was investigated. Adjuvant was found to suppress the generation of cytolytic T cells in vivo when mixed with allogeneic P815 cells before immunization of C57BL/6 mice. Inoculation of the mice with either adjuvant or adjuvant emulsified with allogeneic cells resulted in whole splenic populations or immunoabsorbent-purified T cells that did not generate cytolytic activity in vitro against allogeneic cells. Mixing T cells from normal and adjuvant-treated mice before in vitro sensitization resulted in suppression of lytic activity. However, memory T cells were not subject to the same suppressive regulation as were precytotoxic T cells since adjuvant had no effect on subsequent boosting of memory.

Animals

T and B cell in hapten-specific carrier-determined tolerance.

BDF1 mice were made tolerant by a single i.v. injection of 1 mg of DNAP-gamma1 or by weekly i.v. injections of 0.2 mg of DNP-gamma1 given for a month. In both instances, spleen cells of tolerant animals were fractionated to obtain pure populations of T cells (nonimmunoglobulin-bearing cells), referred to as tolerant T cells, and B cells (immunoglobulin-bearing cells) referred to as tolerant B cells (immunoglobulin-bearing cells) referred to as tolerant B cells. The control cells were similarly fractionated to obtain normal T and B cells. Mixtures of tolerant T cells and normal B cells, or conversely, normal T cells and tolerant B cells were used to repopulate lethally irradiated recipients. These recipients were then immunized with dinitrophenyl-keyhole limpet haemocyanin and in certain instances with other antigen horse red blood cells. The immune response to both antigens was measured using the direct hemolytic plaque assay. It was found that both T and B cells were tolerant and that tolerance was hapten specific at both T- and B-cell levels. While B-cell tolerance was demonstrated at a 1/1 T/B ratio, a 4/1 T/B ratio was necessary to show T-cell tolerance. Thus, the hapten-specific carrier-determined tolerance involves not only B cells but also T cells. The implication of this finding for the cellular mechanism of tolerance in an experimental model closely related to self tolerance is discussed.

Animals

T-cell migration into allografts.

The ability of T and B lymphocytes to migrate into skin allografts undergoing rejection was studied in mice. Spleen cells from CBA/J mice sensitized to transplantation antigens of A/J or C57BL/6 mice were separated on immunabsorbent columns into purified populations of T and B cells, labeled in vitro with 3H-uridine and injected intravenously into CBA/J mice with 7-day old skin iso and allografts (A/J or C57BL/6). The mice were sacrificed 24 h later and studied by autoradiography. After transfer of either unfractionated spleen cells or T cells, large numbers of labeled cells were found in the cellular infiltrate of allografts, whereas extremely few were seen in isografts. In contrast, after transfer of B cells, almost no labeled cells were detected either in the allografts or the isografts, although they, like T cells, homed normally to lymphoid tissue.

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