Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1988 Apr;63(4):625–630.

Active role of T cells in promoting an in vitro autoantibody response to self erythrocytes in NZB mice.

R D Miller 1, C E Calkins 1
PMCID: PMC1454780  PMID: 2966765

Abstract

The in vitro anti-self erythrocyte antibody response of NZB spleen cells appears to be influenced directly by T cells. Thy-1+, L3T4+ helper T cells are required for: (i) the generation in vitro of MRBC-specific IgM and IgG AFC by spleen cells from 'autoimmune' (9-12-month old) NZB mice and (ii) the generation in vitro of MRBC-specific IgM and IgG AFC by spleen cells depleted of suppressor cells from pre-autoimmune (2-3-months-old) NZB mice which show no clinical signs of an anti-MRBC response. It is evident from the present and previous studies that the anti-MRBC autoantibody response is regulated in pre-autoimmune spleen cell populations by Ly2+ T cells. Ly2-T cells from both pre-autoimmune and autoimmune mice in sufficient numbers can overcome this normal regulation and promote the anti-MRBC response in cultures of unfractionated pre-autoimmune spleen cells. Ly2- T cells isolated from autoimmune NZB mice were consistently more active in this than the Ly2- T cells isolated from pre-autoimmune mice, suggesting an enrichment of MRBC-reactive Ly2- T cells in autoimmune NZB mice. The Ly2- T cells from autoimmune NZB mice greatly enhance the autoimmune anti-MRBC response relative to a modest enhancement of the response to a foreign antigen, SRBC, produced by the same cells. These data indicate that T cells play an important role both in supporting the autoantibody response to MRBC and in disrupting tolerance, leading to autoimmunity in NZB mice.

Full text

PDF
625

Selected References

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

  1. Ando D. G., Sercarz E. E., Hahn B. H. Mechanisms of T and B cell collaboration in the in vitro production of anti-DNA antibodies in the NZB/NZW F1 murine SLE model. J Immunol. 1987 May 15;138(10):3185–3190. [PubMed] [Google Scholar]
  2. Calkins C. E., Orbach-Arbouys S., Stutman O., Gershon R. K. Cell interactions in the suppression of in vitro antibody responses. J Exp Med. 1976 Jun 1;143(6):1421–1428. doi: 10.1084/jem.143.6.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cohen P. L., Eisenberg R. A. Anti-Sm autoantibodies in MRL mice: in vitro detection and generation of antibody-forming cells. J Immunol. 1982 Dec;129(6):2682–2685. [PubMed] [Google Scholar]
  4. Cooke A., Hutchings P. R., Playfair J. H. Suppressor T cells in experimental autoimmune haemolytic anaemia. Nature. 1978 May 11;273(5658):154–155. doi: 10.1038/273154a0. [DOI] [PubMed] [Google Scholar]
  5. Cox K. O., Howles A. Induction and regulation of autoimmune hemolytic anemia in mice. Immunol Rev. 1981;55:31–53. doi: 10.1111/j.1600-065x.1981.tb00338.x. [DOI] [PubMed] [Google Scholar]
  6. Deheer D. H., Edginton T. S. Cellular events associated with the immunogenesis of anti-erythrocyte autoantibody responses of NZB mice. Transplant Rev. 1976;31:116–155. doi: 10.1111/j.1600-065x.1976.tb01453.x. [DOI] [PubMed] [Google Scholar]
  7. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  8. Fish F., Ziff M. The in vitro and in vivo induction of anti-double-stranded DNA antibodies in normal and autoimmune mice. J Immunol. 1982 Jan;128(1):409–414. [PubMed] [Google Scholar]
  9. 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]
  10. Gershwin M. E., Castles J. J., Erickson K., Ahmed A. Studies of congenitally immunologic mutant New Zealand mice. II. Absence of T cell progenitor populations and B cell defects of congenitally athymic (nude) New Zealand Black (NZB) mice. J Immunol. 1979 May;122(5):2020–2025. [PubMed] [Google Scholar]
  11. Huston D. P., Steinberg A. D. NZB cytotoxic lymphocyte responses. Kinetic analyses. J Exp Med. 1980 Sep 1;152(3):748–753. doi: 10.1084/jem.152.3.748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Izui S., McConahey P. J., Dixon F. J. Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease. J Immunol. 1978 Dec;121(6):2213–2219. [PubMed] [Google Scholar]
  13. Kelly C. J., Neilson E. G. Contrasuppression in autoimmunity. Abnormal contrasuppression facilitates expression of nephritogenic effector T cells and interstitial nephritis in kdkd mice. J Exp Med. 1987 Jan 1;165(1):107–123. doi: 10.1084/jem.165.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klinman D. M., Steinberg A. D. Proliferation of anti-DNA-producing NZB B cells in a non-autoimmune environment. J Immunol. 1986 Jul 1;137(1):69–75. [PubMed] [Google Scholar]
  15. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  16. Levy M., Fridman W. H., Neauport-Sautes C. In vitro generation of cells producing antierythrocyte autoantibodies in normal mice. Cell Immunol. 1982 Aug;71(2):241–253. doi: 10.1016/0008-8749(82)90259-3. [DOI] [PubMed] [Google Scholar]
  17. Mage M., Mathieson B., Sharrow S., McHugh L., Hämmerling U., Kanellopoulos-Langevin C., Brideau D., Jr, Thomas C. A., 3rd Preparative nonlytic separation of Lyt2+ and Lyt2- T lymphocytes, functional analyses of the separated cells and demonstration of synergy in graft-vs.-host reaction of Lyt2+ and Lyt2- cells. Eur J Immunol. 1981 Mar;11(3):228–235. doi: 10.1002/eji.1830110312. [DOI] [PubMed] [Google Scholar]
  18. Moore J. S., Calkins C. E. In vitro regulation of the pathogenic autoantibody response of New Zealand black mice. I. Loss with age of suppressive activity in T cell populations. J Immunol. 1985 Jun;134(6):3838–3844. [PubMed] [Google Scholar]
  19. Moore J., Calkins C. Formation of antigen specific foci as a complement independent assay for individual antibody-secreting cells. J Immunol Methods. 1983 Oct 28;63(3):377–384. doi: 10.1016/s0022-1759(83)80011-8. [DOI] [PubMed] [Google Scholar]
  20. Moore J., Calkins C. Specific anti-erythrocyte focus formation as a measure of autoantibody secreting cells in NZB mice. Clin Exp Immunol. 1985 Jan;59(1):153–160. [PMC free article] [PubMed] [Google Scholar]
  21. Naysmith J. D., Elson C. J., Dallman M., Fletcher E., Ortega-Pierres M. G. Anti-erythrocyte autoantibody production in mice associated with the injection of rat erythrocytes. Immunology. 1980 Apr;39(4):469–479. [PMC free article] [PubMed] [Google Scholar]
  22. Prud'Homme G. J., Park C. L., Fieser T. M., Kofler R., Dixon F. J., Theofilopoulos A. N. Identification of a B cell differentiation factor(s) spontaneously produced by proliferating T cells in murine lupus strains of the lpr/lpr genotype. J Exp Med. 1983 Feb 1;157(2):730–742. doi: 10.1084/jem.157.2.730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rothermel A. L., Calkins C. E. Effect of antigen priming on T-cell suppression. I. Activity of Ly 1+2+ feedback suppressor T-cell precursors after isolation from competing Ly 2-T cells. Cell Immunol. 1987 Oct 1;109(1):25–38. doi: 10.1016/0008-8749(87)90289-9. [DOI] [PubMed] [Google Scholar]
  24. Sawada S., Talal N. Characteristics of in vitro production of antibodies to DNA in normal and autoimmune mice. J Immunol. 1979 Jun;122(6):2309–2313. [PubMed] [Google Scholar]
  25. Smith H. R., Green D. R., Raveche E. S., Smathers P. A., Gershon R. K., Steinberg A. D. Studies of the induction of anti-DNA in normal mice. J Immunol. 1982 Dec;129(6):2332–2334. [PubMed] [Google Scholar]
  26. Taurog J. D., Smathers P. A., Steinberg A. D. Evidence for abnormalities in separate lymphocyte populations in NZB mice. J Immunol. 1980 Aug;125(2):485–490. [PubMed] [Google Scholar]
  27. Wofsy D., Seaman W. E. Successful treatment of autoimmunity in NZB/NZW F1 mice with monoclonal antibody to L3T4. J Exp Med. 1985 Feb 1;161(2):378–391. doi: 10.1084/jem.161.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES