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. 1976 Sep 1;144(3):662–673. doi: 10.1084/jem.144.3.662

Loss of suppressor T cells in adult NZB/NZW mice

PMCID: PMC2190411  PMID: 1085336

Abstract

We have investigated suppressor T-cell activity in female NZB/NZW F1 mice using PWM-driven IgM biosynthesis in vitro as an indicator system. In initial we studied we observed that spleen cells from normal mice (BALB/c, C57BL/6), as well as from young (4 wk) and adult (18 wk) NZB/NZW mice, cultured in the presence of PWM synthesize 860 +/- 120 ng IgM/10(6) cells/7 days. However, when Con A (at 2 mug/ml) was added directly to the cultures (along with PWM), cells obtained from adult normal mice and young NZB/NZW mice showed a 94% suppression of IgM synthesis, whereas cells obtained from adult NZB/NZW mice were suppressed significantly less. To analyze these findings we studied the effect of Con A-induced suppressor cells (cells cultured with Con A for 24 h and washed free of Con A) on PWM-driven IgM biosynthesis. Spleen cells obtained from normal mice cultured in the presence of Con A- pulsed cells obtained from normal mice and young NZB/NZW mice showed an 83-88% suppression of PWM-driven IgM synthesis. Similarly, supernates obtained from Con A-pulsed cells of normal mice or of young NZB/NZW mice suppressed PWM-driven IgM synthesis. This suppression by Con A- pulsed cells and their supernates required T cells since T-cell fractions but not B-cell fractions eluted from anti-Fab Sephadex columns mediated suppression of co-cultured normal cells; in addition, Con A-pulsed cells treated with anti-theta and complement do not mediate suppression. These studies of Con A-induced suppressor cell activity in normal mice and young NZB/NZW mice contrast with studies of Con A-induced suppressor cell activity in adult NZB/NZW mice. We found that adult NZB/NZW Con A-pulsed cells and supernates obtained from the Con A-pulse cells had vastly decreased suppressor potential; in this case the Con A-pulse cells and supernatant fluids derived from such cells did not suppress PWM-driven IgM synthesis by normal cells. Finally, whereas spleen cells from young and adult NZB/NZW mice differ in their suppressor cell potential, cells from both sources could respond equally to suppressor signals in that Con A-pulsed normal cells or supernates derived from such cells caused equivalent suppression of PWM-driven IgM synthesis by young and adult NZB/NZW cells. These observations allow us to conclude that NZB/NZW mice lose suppressor T- cell activity as they age.

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Selected References

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

  1. Allison A. C., Denman A. M., Barnes R. D. Cooperating and controlling functions of thymus-derived lymphocytes in relation to autoimmunity. Lancet. 1971 Jul 17;2(7716):135–140. doi: 10.1016/s0140-6736(71)92306-3. [DOI] [PubMed] [Google Scholar]
  2. Barthold D. R., Kysela S., Steinberg A. D. Decline in suppressor T cell function with age in female NZB mice. J Immunol. 1974 Jan;112(1):9–16. [PubMed] [Google Scholar]
  3. Barthold D. R., Prescott B., Stashak P. W., Amsbaugh D. F., Baker P. J. Regulation of the antibody response to type 3 pneumococcal polysaccharide. 3. Role of regulatory T cells in the development of an IgG and IgA antibody response. J Immunol. 1974 Mar;112(3):1042–1050. [PubMed] [Google Scholar]
  4. Chess L., MacDermott R. P., Schlossman S. F. Immunologic functions of isolated human lymphocyte subpopulations. I. Quantitative isolation of human T and B cells and response to mitogens. J Immunol. 1974 Oct;113(4):1113–1121. [PubMed] [Google Scholar]
  5. Chused T. M., Steinberg A. D., Parker L. M. Enhanced antibody response of mice to polyinosinic-polycytidylic acid by antithymocyte serum and its age-dependent loss in NZB-W mice. J Immunol. 1973 Jul;111(1):52–57. [PubMed] [Google Scholar]
  6. Dauphinee M. J., Talal N., Goldstein A. L., White A. Thymosin corrects the abnormal DNA synthetic response of NZB mouse thymocytes. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2637–2641. doi: 10.1073/pnas.71.7.2637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dutton R. W. Inhibitory and stimulatory effects of concanavalin A on the response of mouse spleen cell suspensions to antigen. I. Characterization of the inhibitory cell activity. J Exp Med. 1972 Dec 1;136(6):1445–1460. doi: 10.1084/jem.136.6.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dutton R. W. Inhibitory and stimulatory effects of concanavalin A on the response of mouse spleen cell suspensions to antigen. II. Evidence for separate stimulatory and inhibitory cells. J Exp Med. 1973 Dec 1;138(6):1496–1505. doi: 10.1084/jem.138.6.1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gelfand M. C., Parker L. M., Steinberg A. D. Mechanism of allograft rejection in New Zealand mice. II. Role of a serum factor. J Immunol. 1974 Jul;113(1):1–8. [PubMed] [Google Scholar]
  10. Gelfand M. C., Steinberg A. D. Mechanism of allograft rejection in New Zealand mice. I. Cell synergy and its age-dependent loss. J Immunol. 1973 Jun;110(6):1652–1662. [PubMed] [Google Scholar]
  11. Gerber N. L., Hardin J. A., Chused T. M., Steinberg A. D. Loss with age in NZB-W mice of thymic suppressor cells in the graft-vs-host reaction. J Immunol. 1974 Nov;113(5):1618–1625. [PubMed] [Google Scholar]
  12. Gershwin M. E., Ahmed A., Steinberg A. D., Thurman G. B., Goldstein A. L. Correction of T cell function by thymosin in New Zealand mice. J Immunol. 1974 Sep;113(3):1068–1071. [PubMed] [Google Scholar]
  13. Gershwin M. E., Steinberg A. D. Effect of concanavalin A on immunologic abnormalities of New Zealand (NZB/W) mice. Int Arch Allergy Appl Immunol. 1975;48(2):220–224. doi: 10.1159/000231308. [DOI] [PubMed] [Google Scholar]
  14. Kysela S., Steinberg A. D. Increased survival of NZB-W mice given multiple syngeneic young thymus grafts. Clin Immunol Immunopathol. 1973 Nov;2(1):133–136. doi: 10.1016/0090-1229(73)90043-3. [DOI] [PubMed] [Google Scholar]
  15. Parker L. M., Chused T. M., Steinberg A. D. Immunofluorescence studies on thymocytotoxic antibody from New Zealand Black mice. J Immunol. 1974 Jan;112(1):285–292. [PubMed] [Google Scholar]
  16. Playfair J. H. Strain differences in the immune responses of mice. 3. A raised tolerance threshold in NZB thymus cells. Immunology. 1971 Dec;21(6):1037–1043. [PMC free article] [PubMed] [Google Scholar]
  17. Rich R. R., Pierce C. W. Biological expressions of lymphocyte activation : I. Effects of phytomitogens on antibody synthesis in vitro. J Exp Med. 1973 Jan 31;137(2):205–223. doi: 10.1084/jem.137.2.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rich R. R., Pierce C. W. Biological expressions of lymphocyte activation. 3. Suppression of plaque-forming cell responses in vitro by supernatant fluids from concanavalin A-activated spleen cell cultures. J Immunol. 1974 Apr;112(4):1360–1368. [PubMed] [Google Scholar]
  19. Rich R. R., Pierce C. W. Biological expressions of lymphocyte activation. II. Generation of a population of thymus-derived suppressor lymphocytes. J Exp Med. 1973 Mar 1;137(3):649–659. doi: 10.1084/jem.137.3.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rich R. R., Rich S. S. Biological expressions of lymphocyte activation. IV. Concanavalin A-activated suppressor cells in mouse mixed lymphocyte reactions. J Immunol. 1975 Mar;114(3):1112–1115. [PubMed] [Google Scholar]
  21. Staples P. J., Steinberg A. D., Talal N. Induction of immunologic tolerance in older New Zealand mice repopulated with young spleen, bone marrow, or thymus. J Exp Med. 1970 Jun 1;131(6):1223–1238. doi: 10.1084/jem.131.6.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Steinberg A. D. Pathogenesis of autoimmunity in New Zealand mice. V. Loss of thymic suppressor function. Arthritis Rheum. 1974 Jan-Feb;17(1):11–14. doi: 10.1002/art.1780170103. [DOI] [PubMed] [Google Scholar]
  23. Waldmann T. A., Polmar S. H., Balestra S. T., Jost M. C., Bruce R. M., Terry W. D. Immunoglobulin E in immunologic deficiency diseases. II. Serum IgE concentration of patients with acquired hypogammaglobulinemia, thymoma and hypogammaglobulinemia, myotonic dystrophy, intestinal lymphangiectasia and Wiskott-Aldrich syndrome. J Immunol. 1972 Aug;109(2):304–310. [PubMed] [Google Scholar]

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