Abstract
Five out of five allo-specific cytotoxic T lymphocyte (CTL) clones tested strongly suppressed the development of CTLs directed against the H-2 haplotype of the CTL clone and independent of the H-2 specificity recognized by the CTL clone. This was shown by including 100-1,000 cells from the five clones in one way mixed lymphocyte reaction (MLR) cultures in which the stimulator cells were of the same H-2 type as the CTL cells. When these cultures were assayed for cytotoxicity against the stimulator cell haplotype, the cytotoxic activity was decreased in a CTL cell dose-dependent manner by 50 to more than 90%. Suppression was usually not observed in MLR cultures where the CTL-H-2 type was identical with the responder cells or was different from both the responder or stimulator cells. Suppression was demonstrated not to be due to "cold" target inhibition at the time of cytotoxicity assay. Even if the added CTL were completely removed after 48-72 h of culture, significant suppression was obtained. Suppressive ability did not appear to be correlated with the level of allo-specific cytotoxic activity present in the CTL clones, but might involve direct killing of MLR precursor cells by cells in the added CTL clones. The suppression observed here, which is anti-self from the point of view of the added CTL clone, appears to be triggered by precursor cells in the MLR responder population recognizing MHC determinants on cells from the added CTL clone. This peculiar type of suppression, in which the regulator regulates on being recognized, has been christened the veto phenomenon and may play a role in maintenance of self tolerance.
Full Text
The Full Text of this article is available as a PDF (866.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Berke G. Cytotoxic T-lymphocytes. How do they function? Immunol Rev. 1983;72:5–42. doi: 10.1111/j.1600-065x.1983.tb01071.x. [DOI] [PubMed] [Google Scholar]
- Brickell P. M., Latchman D. S., Murphy D., Willison K., Rigby P. W. Activation of a Qa/Tla class I major histocompatibility antigen gene is a general feature of oncogenesis in the mouse. Nature. 1983 Dec 22;306(5945):756–760. doi: 10.1038/306756a0. [DOI] [PubMed] [Google Scholar]
- Brooks C. G., Urdal D. L., Henney C. S. Lymphokine-driven "differentiation" of cytotoxic T-cell clones into cells with NK-like specificity: correlations with display of membrane macromolecules. Immunol Rev. 1983;72:43–72. doi: 10.1111/j.1600-065x.1983.tb01072.x. [DOI] [PubMed] [Google Scholar]
- Fink P. J., Rammensee H. G., Benedetto J. D., Staerz U. D., Lefrancois L., Bevan M. J. Studies on the mechanism of suppression of primary cytotoxic responses by cloned cytotoxic T lymphocytes. J Immunol. 1984 Oct;133(4):1769–1774. [PubMed] [Google Scholar]
- Fink P. J., Rammensee H. G., Bevan M. J. Cloned cytolytic T cells can suppress primary cytotoxic responses directed against them. J Immunol. 1984 Oct;133(4):1775–1781. [PubMed] [Google Scholar]
- Fink P. J., Weissman I. L., Bevan M. J. Haplotype-specific suppression of cytotoxic T cell induction by antigen inappropriately presented on T cells. J Exp Med. 1983 Jan 1;157(1):141–154. doi: 10.1084/jem.157.1.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Glasebrook A. L., Sarmiento M., Loken M. R., Dialynas D. P., Quintans J., Eisenberg L., Lutz C. T., Wilde D., Fitch F. W. Murine T lymphocyte clones with distinct immunological functions. Immunol Rev. 1981;54:225–266. doi: 10.1111/j.1600-065x.1981.tb00439.x. [DOI] [PubMed] [Google Scholar]
- Klein J., Figueroa F., David C. S. H-2 haplotypes, genes and antigens: second listing. II. The H-2 complex. Immunogenetics. 1983;17(6):553–596. doi: 10.1007/BF00366126. [DOI] [PubMed] [Google Scholar]
- Miller R. G. An immunological suppressor cell inactivating cytotoxic T-lymphocyte precursor cells recognizing it. Nature. 1980 Oct 9;287(5782):544–546. doi: 10.1038/287544a0. [DOI] [PubMed] [Google Scholar]
- Muraoka S., Miller R. G. Cells in bone marrow and in T cell colonies grown from bone marrow can suppress generation of cytotoxic T lymphocytes directed against their self antigens. J Exp Med. 1980 Jul 1;152(1):54–71. doi: 10.1084/jem.152.1.54. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muraoka S., Miller R. G. Cells in murine fetal liver and in lymphoid colonies grown from fetal liver can suppress generation of cytotoxic T lymphocytes directed against their self antigens. J Immunol. 1983 Jul;131(1):45–49. [PubMed] [Google Scholar]
- Ozato K., Mayer N. M., Sachs D. H. Monoclonal antibodies to mouse major histocompatibility complex antigens. Transplantation. 1982 Sep;34(3):113–120. doi: 10.1097/00007890-198209000-00001. [DOI] [PubMed] [Google Scholar]
- Rammensee H. G., Juretic A., Nagy Z. A., Klein J. Class I restricted interaction between suppressor and cytolytic cells in the response to minor histocompatibility antigens. J Immunol. 1984 Feb;132(2):668–672. [PubMed] [Google Scholar]
- Rammensee H. G., Nagy Z. A., Klein J. Suppression of cell-mediated lymphocytotoxicity against minor histocompatibility antigens mediated by Lyt-1+Lyt-2+ T cells of stimulator-strain origin. Eur J Immunol. 1982 Nov;12(11):930–934. doi: 10.1002/eji.1830121107. [DOI] [PubMed] [Google Scholar]
- Reimann J., Miller R. G. Differentiation from precursors in athymic nude mouse bone marrow of unusual spontaneously cytolytic cells showing anti-self-H-2 specificity and bearing T cell markers. J Exp Med. 1983 Nov 1;158(5):1672–1692. doi: 10.1084/jem.158.5.1672. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shortman K., Wilson A., Scollay R. Loss of specificity in cytolytic T lymphocyte clones obtained by limit dilution culture of Ly-2+ T cells. J Immunol. 1984 Feb;132(2):584–593. [PubMed] [Google Scholar]
- Simon M. M., Weltzien H. U., Bühring H. J., Eichmann K. Aged murine killer T-cell clones acquire specific cytotoxicity for P815 mastocytoma cells. Nature. 1984 Mar 22;308(5957):367–370. doi: 10.1038/308367a0. [DOI] [PubMed] [Google Scholar]