Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1981 Jun 1;153(6):1547–1561. doi: 10.1084/jem.153.6.1547

Immunoregulatory circuits that modulate responsiveness to suppressor cell signal. Failure of B10 mice to respond to suppressor factors can be overcome by quenching the contrasuppressor circuit

PMCID: PMC2186175  PMID: 6454752

Abstract

The in vitro antibody response of spleen cells from B10 strain mice is not suppressed by factor preparations made by primed Ly-2 T cells, although these preparations can suppress the in vitro antibody response of spleen cells from other mouse strains (1-3)2. The factor preparations from Ly-2 cells contain at least two separable activities: one that acts as a suppressor moiety (Ly-2 T cell suppressor factor [Ly- 2 TsF]) and a second factor that acts as an inducer of contrasuppression (Ly-2 TcsiF); the latter initiates a series of cellular interactions that leads to the inhibition of suppression that we refer to as contrasuppression. Removal of components (either cellular or humoral) of the contrasuppressor circuit makes spleen cells from B10 strain mice as easily suppressible as are those of other mouse strains. Thus, removal of the contrasuppressor inducer cell and/or its biologically active product with the use of an anit-J serum, or removal of the functional acceptor of the inducer cell with the same or other (Ly-2; Qa-1) antisera breaks the B10 suppressor barrier. Contrasuppressive activity. but not helper activity can be eluted from anit-I-J immunoabsorbents. The addition of B10 T cells to either B6 or B10 spleen cell culture deprived of acceptor cells for the TcsiF reconstitutes contrasuppression more efficiently than does the addition of C57BL/6 T cells. Ly-2 TcsiF is more cross-reactive than is Ly-2 TsF so that absorption of factor preparations from sheep erythrocyte-primed Ly-2 cells with horse erythrocytes also breaks the B10 suppressor barrier. The hyperresponsiveness of splenic T cells from B10 strains to Ly-2 TcsiF may be an in vitro exaggeration of a normal in vivo process. Thus it is possible that one can take advantage of this unusual situation to help dissect out the cellular and subcellular components of T cell circuits that moldulate sensitivity to immunoregulatory signals.

Full Text

The Full Text of this article is available as a PDF (848.3 KB).

Selected References

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

  1. Cunningham A. J., Szenberg A. Further improvements in the plaque technique for detecting single antibody-forming cells. Immunology. 1968 Apr;14(4):599–600. [PMC free article] [PubMed] [Google Scholar]
  2. Eisen H. N., Little J. R., Steiner L. A., Simms E. S., Gray W. Degeneracy in the secondary immune response: stimulation of antibody formation by cross-reacting antigens. Isr J Med Sci. 1969 May-Jun;5(3):338–351. [PubMed] [Google Scholar]
  3. Germain R. N., Benacerraf B. Helper and suppressor T cell factors. Springer Semin Immunopathol. 1980 May;3(1):93–127. doi: 10.1007/BF00199927. [DOI] [PubMed] [Google Scholar]
  4. Gershon R. K., Eardley D. D., Durum S., Green D. R., Shen F. W., Yamauchi K., Cantor H., Murphy D. B. Contrasuppression. A novel immunoregulatory activity. J Exp Med. 1981 Jun 1;153(6):1533–1546. doi: 10.1084/jem.153.6.1533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gershon R. K., Kondo K. Degeneracy of the immune response to sheep red cells. Thymic dependency. Immunology. 1972 Sep;23(3):335–342. [PMC free article] [PubMed] [Google Scholar]
  6. Gershon R. K., Kondo K. Degeneracy of the immune response to sheep red cells. Immunology. 1972 Sep;23(3):321–334. [PMC free article] [PubMed] [Google Scholar]
  7. Grey H. M. Phylogeny of immunoglobulins. Adv Immunol. 1969;10:51–104. doi: 10.1016/s0065-2776(08)60415-0. [DOI] [PubMed] [Google Scholar]
  8. Little J. R., Border W., Freidin R. The binding reactions of antibodies specific for the 2,6-dinitrophenyl group. J Immunol. 1969 Oct;103(4):809–817. [PubMed] [Google Scholar]
  9. Little J. R., Eisen H. N. Specificity of the immune response to the 2,4-dinitrophenyl and 2,4,6-trinitrophenyl groups. Ligand binding and fluorescence properties of cross-reacting antibodies. J Exp Med. 1969 Feb 1;129(2):247–265. doi: 10.1084/jem.129.2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mattingly J. A., Kaplan J. M., Janeway C. A., Jr Two distinct antigen-specific suppressor factors induced by the oral administration of antigen. J Exp Med. 1980 Sep 1;152(3):545–554. doi: 10.1084/jem.152.3.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McDougal J. S., Shen F. W., Cort S. P., Bard J. Feedback suppression: phenotypes of T cell subsets involved in the Ly1 T cell-induced immunoregulatory circuit. J Immunol. 1980 Sep;125(3):1157–1160. [PubMed] [Google Scholar]
  12. Murphy D. B., Herzenberg L. A., Okumura K., Herzenberg L. A., McDevitt H. O. A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes. J Exp Med. 1976 Sep 1;144(3):699–712. doi: 10.1084/jem.144.3.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Siskind G. W., Benacerraf B. Cell selection by antigen in the immune response. Adv Immunol. 1969;10:1–50. doi: 10.1016/s0065-2776(08)60414-9. [DOI] [PubMed] [Google Scholar]
  14. Sy M. S., Miller S. D., Moorhead J. W., Claman H. N. Active suppression of 1-fluoro-2,4-dinitrobenzene-immune T cells. Requirement of an auxiliary T cell induced by antigen. J Exp Med. 1979 May 1;149(5):1197–1207. doi: 10.1084/jem.149.5.1197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Taniguchi M., Tada T., Tokuhisa T. Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. III. Dual gene control of the T-cell-mediated suppression of the antibody response. J Exp Med. 1976 Jul 1;144(1):20–31. doi: 10.1084/jem.144.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Underdown B. J., Eisen H. N. Cross-reactions between 2,4-dinitrophenyl and 5-acetouracil groups. J Immunol. 1971 Jun;106(6):1431–1440. [PubMed] [Google Scholar]
  17. Walker J. G., Siskind G. W. Studies on the control of antibody synthesis. Effect of antibody affinity upon its ability to suppress antibody formation. Immunology. 1968 Jan;14(1):21–28. [PMC free article] [PubMed] [Google Scholar]
  18. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES