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M Röllinghoff

Publications and source records attributed to M Röllinghoff.

At least 217 records · Page 12Linked to original sources

Cell-mediated allograft responses in vitro. VI. Studies on macrophage-mediated cytotoxicity.

Normal murine peritoneal macrophages were rendered cytotoxic against 51Cr-labelled allogeneic and syngeneic target cells by incubation with supernatant of selected cell cultures.'Active' culture supernatant was produced both by specifically sensitized cytotoxic T lymphocytes as well as by mitogen-stimulated T cells, but not by mitogen-stimulated B cells. The in vitro induced macrophage-mediated cytotoxicity was found to be non-specific in the sense that 51Cr-labelled target cells of different H-2 haplotype were lysed equally well.

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The allogeneic effect: M-locus differences substitute for differences in the H-2 major histocompatibility complex.

The primary immune response against sheep red blood cells in T cell-deficient spleen cell cultures from nude mice was tested in the absence and presence of allogeneic spleen cells. The allogeneic spleen cells differed either in regard to the major histocompatibility complex (H-2) or only with respect to the M-locus. Surprisingly the M-locus different spleen cells were almost as efficient in enhancing the anti-sheep red blood cell response in nude cultures as were the cells differing on the complete H-2 complex. Evidence is presented that AKR anti-theta serum sensitive T cells are responsible for the M-locus-dependent effect edscribed. This effect is shown to be mediated by a factor released from actived T cells stimulated in M-locus different mixed lymphocyte cultures. Since almost identical parameters have been observed in both the M-locus-dependent situation as in the "classical" allogeneic situation we concluded that an allogeneic effect can be induced by T cells responding to a complete set of the major histocompatibility complex (H-2) as well as to lymphocyte-activating determinants (M-locus) alone.

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The cytotoxic activity of mouse T lymphocytes against allogeneic cytotoxic T cells.

Using a 51Cr cytotoxicity assay, the sensitivity of murine cytotoxic T cells to T cell mediated cytotoxicity has been tested. Two experimental approaches have been used. First, cytotoxic T-blast-lymphocytes (CTBL), enriched by the velocity sedimentation at 1 g were used both as cytotoxic effector cells and as 51Cr-labelled target cells. It was found that murine CTBL are capable to lyse directly and specifically allogeneic CTBL within 200 minutes. The second approach used was to incubate CTBL together with CTBL, the cytotoxic activity of which was directed against the transplantation antigens of the added allogeneic CTBL population. After 10 hours, the residual cytotoxic activity was tested. Again it was found that CTBL were capable of functionally inactivating allogeneic CTBL. Therefore the results obtained are incompatible with the concept that target cell lysis by cytotoxic T lymphocytes is mediated by a non specific "lymphotoxin", secreted by activated T cells after the antigen-recognition phase in the confined space between T cells and target cells.

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In vitro induction of tumor-specific immunity. I. Parameters of activation and cytotoxic reactivity of mouse lymphoid cells immunized in vitro against syngeneic and allogeneic plasma cell tumors.

Induction of tumor-specific immunity in vitro was accomplished by cocultivation of cortisone-resistant murine thymocytes or spleen cells with irradiated syngeneic plasma cell tumors (PCT). The cytotoxic activity generated could be detected in a short-term (51)Cr-release assay. Optimal cytotoxic activity against PCT-associated transplantation antigens (TATA) was generated after 7 days in culture. Unlike cytotoxic responses to tumor allografts in which the cytotoxic activity was directed against allogeneic transplantation antigens, the cytotoxic activity obtained in the syngeneic tumor system was specific to the immunizing syngeneic PCT. Similar parameters of induction of cytotoxic responses in in vitro tumor allograft responses and in the syngeneic tumor system suggested that both reactions are cell-mediated cytotoxic immune responses. With regard to the magnitude of cytotoxic responses obtained, allogeneic transplantation antigens induced about a 30-fold higher cytotoxic immune response than plasma cell TATA. The results are consistent with the concept that in vitro tumor allograft responses and in vitro responses against TATA of PCT are similar in quality, but differ in the magnitude of the cytotoxic response provoked.

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