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K Pfizenmaier

Publications and source records attributed to K Pfizenmaier.

150 records · Page 9Linked to original sources

Cell-mediated immunity in lumphocytic choriomeningitis. I. The specificity of the cytotoxic T lymphocytes.

The specificity of cytotoxic T lymphocytes (CTL) generated during murine lymphocytic choriomeningitis (LCM) has been investigated. CTL were obtained from the spleens of mice injected i.p. with LCM virus. The cytotoxic activity of the CTL was tested in an in vitro 51Cr cytotoxicity assay using infected macrophages or fibroblasts as target cells. At the peak of the cytotoxic T cell response (7-8 days after infection) the cytotoxic action was restricted to syngeneic virus-infected target cells. Using H-2 recombinant mice the target antigen of the CTL generated could be identified as products coded for by either the H-2 K or H-2 D region of the major histocompatibility complex. I region identity between CTL and infected target cells was insufficient for optimal lysis to occur. During the early phase of LCM virus infection there was a transient phase during which non-infected H-2 histocompatible targets were lysed as efficiently as virus-infected target cells. This finding may suggest, that during the early phase of LCM disease self-reactive cytotoxic T lymphocytes are temporarily present in LCM virus-infected mice.

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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 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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Post-transcriptional downregulation of MHC class I expression in oncogene-transformed cells is reverted by IFN-gamma and TNF-alpha.

Transformation of murine NIH3T3 fibroblasts with retroviral vectors carrying the mos, myc and the Ha-ras oncogene, respectively, was associated with a strong reduction of H2 antigen expression in the cell membrane. Analysis of H-2K and beta 2-microglobulin promoter-driven CAT activity in these oncogenic transformants and normal NIH3T3 fibroblasts revealed unchanged promoter activity, suggesting post-transcriptional control of MHC class I expression by these oncogenes. Treatment with IFN-gamma and TNF-alpha caused 2- to 3-fold enhancement of H-2K and beta 2-microglobulin promoter activity, as well as a normalization (TNF-alpha treatment) or enhancement (IFN-gamma treatment) of H2 membrane expression. These data suggest that IFN-gamma as well as TNF-alpha can counteract downregulation of H-2 genes by interference with an oncogene-induced, post-transcriptional block as well as by a direct enhancement of H-2 gene transcription.

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