Abstract
Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to “modified self” are verified in several C57BL/10 congenic and B10.A recombinant mouse strains.
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Selected References
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- Abbasi K., Démant P., Festenstein H., Holmes J., Huber B., Rychiková M. Mouse mixed lymphocyte reactions and cell-mediated lympholysis: genetic control and relevance to antigenic strength. Transplant Proc. 1973 Dec;5(4):1329–1337. [PubMed] [Google Scholar]
- Alter B. J., Bach F. H. Role of H-2 lymphocyte-defined and serologically-defined components in the generation of cytotoxic lymphocytes. J Exp Med. 1974 Nov 1;140(5):1410–1415. doi: 10.1084/jem.140.5.1410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alter B. J., Schendel D. J., Bach M. L., Bach F. H., Klein J., Stimpfling J. H. Cell-mediated lympholysis. Importance of serologically defined H-2 regions. J Exp Med. 1973 May 1;137(5):1303–1309. doi: 10.1084/jem.137.5.1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fathman C. G., Handwerger B. S., Sachs D. H. Evidence for a role of Ir-associated alloantigens in mixed lymphocyte culture stimulation. J Exp Med. 1974 Sep 1;140(3):853–858. doi: 10.1084/jem.140.3.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nabholz M., Vives J., Young H. M., Meo T., Miggiano V., Rijnbeek A., Shreffler D. C. Cell-mediated cell lysis in vitro: genetic control of killer cell production and target specificities in the mouse. Eur J Immunol. 1974 May;4(5):378–387. doi: 10.1002/eji.1830040514. [DOI] [PubMed] [Google Scholar]
- Plate J. M., McKenzie I. F. "B"-cell stimulation of allogeneic T-cell proliferation in mixed lymphocyte cultures. Nat New Biol. 1973 Oct 24;245(147):247–249. doi: 10.1038/newbio245247a0. [DOI] [PubMed] [Google Scholar]
- Schendel D. J., Bach F. H. Genetic control of cell-mediated lympholysis in mouse. J Exp Med. 1974 Dec 1;140(6):1534–1546. doi: 10.1084/jem.140.6.1534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shearer G. M. Cell-mediated cytotoxicity to trinitrophenyl-modified syngeneic lymphocytes. Eur J Immunol. 1974 Aug;4(8):527–533. doi: 10.1002/eji.1830040802. [DOI] [PubMed] [Google Scholar]