Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1976 Aug 1;144(2):398–413. doi: 10.1084/jem.144.2.398

Heterogeneity of murine regulatory T cells. I. Subpopulations of amplifier and suppressor T cells

PMCID: PMC2190376  PMID: 1085327

Abstract

Immunization of C3H/HeJ mice with 4 X 10(9) SRBC yields a whole splenic T-cell population which can, upon transfer, specifically suppress recipient direct and indirect plaque-forming cells (PFC) responses to sheep erythrocytes (SRBC). Discontinuous bovine serum albumin density gradient fractionation of these T cells demonstrated a population of low density T cells which augmented and a population of high density T cells which suppressed recipient responses irrespective of the number of T cells transferred. Moreover, infusion of admixtures of low and high density cells resulted in intermediate regulatory functions which could be predicted by knowing the regulatory capacity of each population alone. In addition to heterogeneity existing among regulatory T cells as regards amplification and suppression, it appeared that heterogeneity existed within the suppressor T population. Thus, T cells capable of inhibiting direct PFC could be distinguished from those suppressing indirect PFC by their differential localization in peripheral lymphoid tissue, differences in the dissipation of suppressive influences during incubation at 37 degrees C, and by differences in the possible requirement for adherent cell populations. While the relative frequency of both low density amplifier and high density suppressor cells increased with the dose of SRBC used for their induction, it appeared that suppressor cells might be generated in response to feedback signals from amplifier cells. These studies indicate that further delineation of heterogeneity existing within suppressor populations may be helpful in defining mechanisms required for the induction and manifestation of suppressive regulatory forces.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

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

  1. Baker P. J. Homeostatic control of antibody responses: a model based on the recognition of cell-associated antibody by regulatory T cells. Transplant Rev. 1975;26:3–20. doi: 10.1111/j.1600-065x.1975.tb00172.x. [DOI] [PubMed] [Google Scholar]
  2. Basten A., Miller J. F., Sprent J., Cheers C. Cell-to-cell interaction in the immune response. X. T-cell-dependent suppression in tolerant mice. J Exp Med. 1974 Jul 1;140(1):199–217. doi: 10.1084/jem.140.1.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Basten A., Miller J. F., Warner N. L., Abraham R., Chia E., Gamble J. A subpopulation of T cells bearing Fc receptors. J Immunol. 1975 Oct;115(4):1159–1165. [PubMed] [Google Scholar]
  4. Benjamin D. C. Evidence for specific suppression in the maintenance of immunologic tolerance. J Exp Med. 1975 Mar 1;141(3):635–646. doi: 10.1084/jem.141.3.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benson M. D., Aldo-Benson M. A., Shirahama T., Borel Y., Cohen A. S. Suppression of in vitro antibody response by a serum factor (SAA) in experimentally induced amyloidosis. J Exp Med. 1975 Jul 1;142(1):236–241. doi: 10.1084/jem.142.1.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Eardley D. D., Gershon R. K. Feedback induction of suppressor T-cell activity. J Exp Med. 1975 Aug 1;142(2):524–529. doi: 10.1084/jem.142.2.524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Feldmann M., Beverley P. C., Dunkley M., Kontiainen S. Different Ly antigen phenotypes of in vitro induced helper and suppressor cells. Nature. 1975 Dec 18;258(5536):614–616. doi: 10.1038/258614a0. [DOI] [PubMed] [Google Scholar]
  9. Gerber N. L., Steinberg A. D. Physical separation of "suppressor" from "helper" thymocytes. J Immunol. 1975 Dec;115(6):1744–1745. [PubMed] [Google Scholar]
  10. Gershon R. K. A disquisition on suppressor T cells. Transplant Rev. 1975;26:170–185. doi: 10.1111/j.1600-065x.1975.tb00179.x. [DOI] [PubMed] [Google Scholar]
  11. Gershon R. K., Kondo K. Infectious immunological tolerance. Immunology. 1971 Dec;21(6):903–914. [PMC free article] [PubMed] [Google Scholar]
  12. Gershon R. K., Lance E. M., Kondo K. Immuno-regulatory role of spleen localizing thymocytes. J Immunol. 1974 Feb;112(2):546–554. [PubMed] [Google Scholar]
  13. Gershon R. K., Maurer P. H., Merryman C. F. A cellular basis for genetically controlled immunologic unresponsiveness in mice: tolerance induction in T-cells. Proc Natl Acad Sci U S A. 1973 Jan;70(1):250–254. doi: 10.1073/pnas.70.1.250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gershon R. K., Mokyr M. B., Mitchell M. S. Activation of suppressor T cells by tumour cells and specific antibody. Nature. 1974 Aug 16;250(467):594–596. doi: 10.1038/250594a0. [DOI] [PubMed] [Google Scholar]
  15. Janeway C. A., Jr Cellular cooperation during in vivo anti-hapten antibody responses. I. The effect of cell number on the response. J Immunol. 1975 Apr;114(4):1394–1401. [PubMed] [Google Scholar]
  16. 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]
  17. Kettman J., Mathews M. C. Radioresistance of cells responsible for delayed hypersensitivity reactions in the mouse. J Immunol. 1975 Aug;115(2):606–608. [PubMed] [Google Scholar]
  18. Menzoian J. O., Glasgow A. H., Nimberg R. D., Cooperband S. R., Schmid K., Saporoschetz I., Mannick J. A. Regulation of T lymphocyte function by immunoregulatory alphaglobulin (IRA). J Immunol. 1974 Jul;113(1):266–273. [PubMed] [Google Scholar]
  19. Mortensen R. F., Osmand A. P., Gewurz H. Effects on C-reactive protein on the lymphoid system. I. Binding to thymus-dependent lymphocytes and alteration of their functions. J Exp Med. 1975 Apr 1;141(4):821–839. [PMC free article] [PubMed] [Google Scholar]
  20. Murgita R. A., Tomasi T. B., Jr Suppression of the immune response by alpha-fetoprotein on the primary and secondary antibody response. J Exp Med. 1975 Feb 1;141(2):269–286. doi: 10.1084/jem.141.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Raidt D. J., Mishell R. I., Dutton R. W. Cellular events in the immune response : analysis and in vitro response of mouse spleen cell populations separated by differential flotation in albumin gradients. J Exp Med. 1968 Oct 1;128(4):681–698. doi: 10.1084/jem.128.4.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Scavulli J., Dutton R. W. Competition between concanavalin A-induced stimulatory and inhibitory effects in the in vitro immune response to antigen. J Exp Med. 1975 Feb 1;141(2):524–529. doi: 10.1084/jem.141.2.524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sinclair N. R., Lees R. K., Abrahams S., Chan P. L., Fagan G., Stiller C. R. Regulation of the immune response. X. Antigen-antibody complex inactivation of cells involved in adoptive transfer. J Immunol. 1974 Nov;113(5):1493–1500. [PubMed] [Google Scholar]
  24. Stobo J. D., Rosenthal A. S., Paul W. E. Functional heterogeneity of murine lymphoid cells. V. Lymphocytes lacking detectable surface theta or immunoglobulin determinants. J Exp Med. 1973 Jul 1;138(1):71–88. doi: 10.1084/jem.138.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stout R. D., Herzenberg L. A. The Fc receptor on thymus-derived lymphocytes: II. Mitogen responsiveness of T lymphocytes bearing the Fc receptor. J Exp Med. 1975 Nov 1;142(5):1041–1051. doi: 10.1084/jem.142.5.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tada T., Takemori T. Selective roles of thymus-derived lymphocytes in the antibody response. I. Differential suppressive effect of carrier-primed T cells on hapten-specific IgM and IgG antibody responses. J Exp Med. 1974 Jul 1;140(1):239–252. doi: 10.1084/jem.140.1.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wu C-Y, Lance E. M. Immunoregulation by spleen-seeking thymocytes. II. Role in the response to sheep erythrocytes. Cell Immunol. 1974 Jul;13(1):1–11. doi: 10.1016/0008-8749(74)90221-4. [DOI] [PubMed] [Google Scholar]

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

RESOURCES