Skip to main content
Immunology logoLink to Immunology
. 1980 Jan;39(1):93–99.

Inhibition of the activity of cytotoxic murine T lymphocytes by antibodies to idiotypic determinants.

R Rabinowitz, M Schlesinger
PMCID: PMC1457787  PMID: 6155324

Abstract

The nature of the receptors on the surface of cytotoxic T lymphocytes (CTL), which enable these cells to recognize antigens on allogeneic targets, is still a matter of controversy. In the present study various mouse alloantisera were tested for their capacity to inhibit, in the absence of complement, the cytotoxic activity of sensitized peritoneal T lymphocytes. The only antiserum which, even after heat inactivation, consistently inhibited cytotoxic T lymphocytes was an antiserum elicited in (C3H X C57B1/6)F1 mice by immunization with AKR/Cum thymus cells. The serum inhibited the cytotoxic reaction of either AKR/J or AKR/Cum CTL on EL-4 target cells but had no inhibitory activity on the cytotoxic reaction of AKR/J cells against P-815 target cells. Thus the inhibitory activity of the serum could not be attributed to antibodies against Ly-3 determinants present in the serum. This conclusion was strengthened by the finding that the inhibitory activity of the serum could be removed by absorption, not only with AKR/J thymus cells but also with AKR/J bone-marrow cells, a procedure which did not affect the titre of Ly-3 antibodies. The serum failed to exert any inhibition on cytotoxic T lymphocytes of BALB/c and C3H mice reacting against EL-4 target cells, indicating that the inhibitory activity of the antiserum did not result from contamination by antibodies against C57B1 antigenic determinants. It was concluded that the inhibitory activity of the antiserum resulted from the presence of antibodies against idiotypic determinants expressed on AKR/Cum thymus cells reacting against the hybrid hosts. It seems, therefore, that idiotypic determinants expressed on the surface of cytotoxic T lymphocytes may be directly involved in their cytotoxic activity.

Full text

PDF
93

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. Binz H., Askonas B. A. Inhibition of mixed leukocyte culture by anti-idiotypic antibodies. Eur J Immunol. 1975 Sep;5(9):618–623. doi: 10.1002/eji.1830050908. [DOI] [PubMed] [Google Scholar]
  3. Binz H., Wigzell H. Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. I. Demonstration of similar or identical idiotypes on IgG molecules and T-cell receptors with specificity for the same alloantigens. J Exp Med. 1975 Jul 1;142(1):197–211. doi: 10.1084/jem.142.1.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Binz H., Wigzell H. Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. II. Determination of frequency and characteristics of idiotypic T and B lymphocytes in normal rats using direct visualization. J Exp Med. 1975 Nov 1;142(5):1218–1230. doi: 10.1084/jem.142.5.1218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Black S. J., Hämmerling G. J., Berek C., Rajewsky K., Eichmann K. Idiotypic analysis of lymphocytes in vitro. I. Specificity and heterogeneity of B and T lymphocytes reactive with anti-idiotypic antibody. J Exp Med. 1976 Apr 1;143(4):846–860. doi: 10.1084/jem.143.4.846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohen A., Schlesinger M. Absorption of guinea pig serum with agar. A method for elimination of itscytotoxicity for murine thymus cells. Transplantation. 1970 Jul;10(1):130–132. doi: 10.1097/00007890-197007000-00027. [DOI] [PubMed] [Google Scholar]
  7. Feldman M., Cohen I. R., Wekerle H. T-cell mediated immunity in vitro: an analysis of antigen recognition and target cell lysis. Transplant Rev. 1972;12:57–90. doi: 10.1111/j.1600-065x.1972.tb00053.x. [DOI] [PubMed] [Google Scholar]
  8. Fishelson Z., Berke G. T lymphocyte-mediated cytolysis: dissociation of the binding and lytic mechanisms of the effector cell. J Immunol. 1978 Apr;120(4):1121–1126. [PubMed] [Google Scholar]
  9. Henney C. S. On the mechanism of T-cell mediated cytolysis. Transplant Rev. 1973;17(0):37–70. doi: 10.1111/j.1600-065x.1973.tb00123.x. [DOI] [PubMed] [Google Scholar]
  10. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  11. Kimura A. K. Inhibition of specific cell-mediated cytotoxicity by anti-T-cell receptor antibody. J Exp Med. 1974 Apr 1;139(4):888–901. doi: 10.1084/jem.139.4.888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Krammer P. H. Alloantigen receptors on activated T cells in mice. I. Binding of alloantigens and anti-idiotypic antibodies to the same receptors. J Exp Med. 1978 Jan 1;147(1):25–36. doi: 10.1084/jem.147.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kuettner M. G., Wang A. L., Nisonoff A. Quantitative investigations of idiotypic antibodies. VI. Idiotypic specificity as a potential genetic marker for the variable regions of mouse immunoglobulin polypeptide chains. J Exp Med. 1972 Mar 1;135(3):579–595. doi: 10.1084/jem.135.3.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kuppers R. C., Henney C. S. Studies on the mechanism of lymphocyte-mediated cytolysis. IX. Relationships between antigen recognition and lytic expression in killer T cells. J Immunol. 1977 Jan;118(1):71–76. [PubMed] [Google Scholar]
  15. Marchalonis J. J., Cone R. E. Biochemical and biological characteristics of lymphocyte surface immunoglobulin. Transplant Rev. 1973;14:3–49. doi: 10.1111/j.1600-065x.1973.tb00101.x. [DOI] [PubMed] [Google Scholar]
  16. Martz E. Mechanism of specific tumor-cell lysis by alloimmune T lymphocytes: resolution and characterization of discrete steps in the cellular interaction. Contemp Top Immunobiol. 1977;7:301–361. doi: 10.1007/978-1-4684-3054-7_9. [DOI] [PubMed] [Google Scholar]
  17. Moroz C., Hahn Y. Cell-surface immunoglobulin human thymus cells and its biosynthesis in vitro. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3716–3720. doi: 10.1073/pnas.70.12.3716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Ramseier H., Aguet M., Lindenmann J. Similarity of idiotypic determinants of T-and B-lymphocyte receptors for alloantigens. Immunol Rev. 1977;34:50–88. doi: 10.1111/j.1600-065x.1977.tb00368.x. [DOI] [PubMed] [Google Scholar]
  20. Ramseier H., Lindenmann J. Similarity of cellular recognition structures for histocompatibility antigens and of combining sites of corresponding alloantibodies. Eur J Immunol. 1972 Apr;2(2):109–114. doi: 10.1002/eji.1830020203. [DOI] [PubMed] [Google Scholar]
  21. Roelants G., Forni L., Pernis B. Blocking and redistribution ("capping") of antigen receptors on T and B lymphocytes by anti-immunoglobulin antibody. J Exp Med. 1973 Apr 1;137(4):1060–1077. doi: 10.1084/jem.137.4.1060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schlesinger M., Hurvitz D. Characterization of cytotoxic isoantisera produced in R3 mice. I. Demonstration of antibodies against the theta-C3H isoantigen. Transplantation. 1969 Feb;7(2):132–141. doi: 10.1097/00007890-196902000-00006. [DOI] [PubMed] [Google Scholar]
  23. Schwartz M., Lifshitz R., Givol D., Mozes E., Haimovich J. Cross-reactive idiotypic determinants on murine anti-(T,G)-A--L antibodies. J Immunol. 1978 Aug;121(2):421–426. [PubMed] [Google Scholar]
  24. Shiku H., Kisielow P., Bean M. A., Takahashi T., Boyse E. A., Oettgen H. F., Old L. J. Expression of T-cell differentiation antigens on effector cells in cell-mediated cytotoxicity in vitro. Evidence for functional heterogeneity related to the surface phenotype of T cells. J Exp Med. 1975 Jan 1;141(1):227–241. doi: 10.1084/jem.141.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wigzell H., Häyry P. Specific fractionation of immunocompetent cells. Application in the analysis of effector cells involved in cell mediated lysis. Curr Top Microbiol Immunol. 1974;67:1–42. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES