Abstract
Mechanisms of T cell-mediated cytotoxicity remain poorly defined at the molecular level. To investigate some of these mechanisms, we used as target cells, on the one hand, thymocytes from lpr and gld mouse mutants, and on the other hand, L1210 cells transfected or not with the apoptosis-inducing Fas molecule. These independent mutant or transfectant-based approaches both led to the conclusion that Fas was involved in the Ca(2+)-independent component of cytotoxicity mediated by at least two sources of T cells, namely nonantigen-specific in vitro activated hybridoma cells, and antigen-specific in vivo raised peritoneal exudate lymphocytes. Thus, in these cases, T cell-mediated cytotoxicity involved transduction via Fas of the target cell death signal.
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- Allen R. D., Marshall J. D., Roths J. B., Sidman C. L. Differences defined by bone marrow transplantation suggest that lpr and gld are mutations of genes encoding an interacting pair of molecules. J Exp Med. 1990 Nov 1;172(5):1367–1375. doi: 10.1084/jem.172.5.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berke G., Sullivan K. A., Amos B. Rejection of ascites tumor allografts. I. Isolation, characterization, and in vitro reactivity of peritoneal lymphoid effector cells from BALB-c mice immune to EL4 leukosis. J Exp Med. 1972 Jun 1;135(6):1334–1350. doi: 10.1084/jem.135.6.1334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen J. J., Duke R. C., Chervenak R., Sellins K. S., Olson L. K. DNA fragmentation in targets of CTL: an example of programmed cell death in the immune system. Adv Exp Med Biol. 1985;184:493–508. doi: 10.1007/978-1-4684-8326-0_32. [DOI] [PubMed] [Google Scholar]
- Conzelmann A., Corthésy P., Cianfriglia M., Silva A., Nabholz M. Hybrids between rat lymphoma and mouse T cells with inducible cytolytic activity. Nature. 1982 Jul 8;298(5870):170–172. doi: 10.1038/298170a0. [DOI] [PubMed] [Google Scholar]
- Davidson W. F., Dumont F. J., Bedigian H. G., Fowlkes B. J., Morse H. C., 3rd Phenotypic, functional, and molecular genetic comparisons of the abnormal lymphoid cells of C3H-lpr/lpr and C3H-gld/gld mice. J Immunol. 1986 Jun 1;136(11):4075–4084. [PubMed] [Google Scholar]
- Debatin K. M., Goldmann C. K., Bamford R., Waldmann T. A., Krammer P. H. Monoclonal-antibody-mediated apoptosis in adult T-cell leukaemia. Lancet. 1990 Mar 3;335(8688):497–500. doi: 10.1016/0140-6736(90)90735-n. [DOI] [PubMed] [Google Scholar]
- Decker T., Lohmann-Matthes M. L., Gifford G. E. Cell-associated tumor necrosis factor (TNF) as a killing mechanism of activated cytotoxic macrophages. J Immunol. 1987 Feb 1;138(3):957–962. [PubMed] [Google Scholar]
- Erard F., Corthesy P., Smith K. A., Fiers W., Conzelmann A., Nabholz M. Characterization of soluble factors that induce the cytolytic activity and the expression of T cell growth factor receptors of a T cell hybrid. J Exp Med. 1984 Aug 1;160(2):584–599. doi: 10.1084/jem.160.2.584. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ichinose Y., Bakouche O., Tsao J. Y., Fidler I. J. Tumor necrosis factor and IL-1 associated with plasma membranes of activated human monocytes lyse monokine-sensitive but not monokine-resistant tumor cells whereas viable activated monocytes lyse both. J Immunol. 1988 Jul 15;141(2):512–518. [PubMed] [Google Scholar]
- Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
- Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kinkhabwala M., Sehajpal P., Skolnik E., Smith D., Sharma V. K., Vlassara H., Cerami A., Suthanthiran M. A novel addition to the T cell repertory. Cell surface expression of tumor necrosis factor/cachectin by activated normal human T cells. J Exp Med. 1990 Mar 1;171(3):941–946. doi: 10.1084/jem.171.3.941. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kobayashi N., Hamamoto Y., Yamamoto N., Ishii A., Yonehara M., Yonehara S. Anti-Fas monoclonal antibody is cytocidal to human immunodeficiency virus-infected cells without augmenting viral replication. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9620–9624. doi: 10.1073/pnas.87.24.9620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kriegler M., Perez C., DeFay K., Albert I., Lu S. D. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell. 1988 Apr 8;53(1):45–53. doi: 10.1016/0092-8674(88)90486-2. [DOI] [PubMed] [Google Scholar]
- Liu C. C., Detmers P. A., Jiang S. B., Young J. D. Identification and characterization of a membrane-bound cytotoxin of murine cytolytic lymphocytes that is related to tumor necrosis factor/cachectin. Proc Natl Acad Sci U S A. 1989 May;86(9):3286–3290. doi: 10.1073/pnas.86.9.3286. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacLennan I. C., Gotch F. M., Golstein P. Limited specific T-cell mediated cytolysis in the absence of extracellular Ca2+. Immunology. 1980 Jan;39(1):109–117. [PMC free article] [PubMed] [Google Scholar]
- Oehm A., Behrmann I., Falk W., Pawlita M., Maier G., Klas C., Li-Weber M., Richards S., Dhein J., Trauth B. C. Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. J Biol Chem. 1992 May 25;267(15):10709–10715. [PubMed] [Google Scholar]
- Owen-Schaub L. B., Yonehara S., Crump W. L., 3rd, Grimm E. A. DNA fragmentation and cell death is selectively triggered in activated human lymphocytes by Fas antigen engagement. Cell Immunol. 1992 Mar;140(1):197–205. doi: 10.1016/0008-8749(92)90187-t. [DOI] [PubMed] [Google Scholar]
- Piontek G. E., Taniguchi K., Ljunggren H. G., Grönberg A., Kiessling R., Klein G., Kärre K. YAC-1 MHC class I variants reveal an association between decreased NK sensitivity and increased H-2 expression after interferon treatment or in vivo passage. J Immunol. 1985 Dec;135(6):4281–4288. [PubMed] [Google Scholar]
- Russell J. H., Masakowski V., Rucinsky T., Phillips G. Mechanisms of immune lysis. III. Characterization of the nature and kinetics of the cytotoxic T lymphocyte-induced nuclear lesion in the target. J Immunol. 1982 May;128(5):2087–2094. [PubMed] [Google Scholar]
- Tirosh R., Berke G. T-Lymphocyte-mediated cytolysis as an excitatory process of the target. I. Evidence that the target cell may be the site of Ca2+ action. Cell Immunol. 1985 Oct 1;95(1):113–123. doi: 10.1016/0008-8749(85)90300-4. [DOI] [PubMed] [Google Scholar]
- Trauth B. C., Klas C., Peters A. M., Matzku S., Möller P., Falk W., Debatin K. M., Krammer P. H. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science. 1989 Jul 21;245(4915):301–305. doi: 10.1126/science.2787530. [DOI] [PubMed] [Google Scholar]
- Watanabe-Fukunaga R., Brannan C. I., Copeland N. G., Jenkins N. A., Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992 Mar 26;356(6367):314–317. doi: 10.1038/356314a0. [DOI] [PubMed] [Google Scholar]
- Watanabe-Fukunaga R., Brannan C. I., Itoh N., Yonehara S., Copeland N. G., Jenkins N. A., Nagata S. The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J Immunol. 1992 Feb 15;148(4):1274–1279. [PubMed] [Google Scholar]
- Wyllie A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980 Apr 10;284(5756):555–556. doi: 10.1038/284555a0. [DOI] [PubMed] [Google Scholar]
- Yonehara S., Ishii A., Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med. 1989 May 1;169(5):1747–1756. doi: 10.1084/jem.169.5.1747. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Boehmer H., Hengartner H., Nabholz M., Lernhardt W., Schreier M. H., Haas W. Fine specificity of a continuously growing killer cell clone specific for H-Y antigen. Eur J Immunol. 1979 Aug;9(8):592–597. doi: 10.1002/eji.1830090804. [DOI] [PubMed] [Google Scholar]