Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1981 Sep 1;154(3):791–808. doi: 10.1084/jem.154.3.791

Analysis of T cell function in autoimmune murine strains. Defects in production and responsiveness to interleukin 2

PMCID: PMC2186441  PMID: 6456321

Abstract

In the studies reported here, we have analyzed the production and consumption of T cell growth factor, more recently termed interleukin 2 (IL-2), as well as some cell-mediated immune functions, in murine strains [MRL, BXSB, NZB, and (NZB x NZWF1] manifesting systemic lupus erythematosus (SLE)-like syndromes. Young (4-6 wk) or old (4-8 mo) autoimmune or normal mice were studied and compared with regard to the following T cell functions in vitro after stimulation with concanavalin A (Con A): (a) mitogenic response; (b) IL-2 levels in culture supernates; and (c) the ability to respond to and adsorb IL-2. In addition, proliferative activity in the allogeneic mixed leukocyte culture and frequency of alloreactive cytotoxic T lymphocyte precursors (CTLp) were analyzed in some of these strains. Reduced Con A-induced mitogenic responses and IL-2 production appeared at 3-6 wk of age in the early, severe SLE developing strains MRL-Mp-lpr/lpr (MRL/l) and male BXSB and progressed thereafter. Similar defects appeared at a later stage in MRL/Mp-+/+ and (NZB x NZW)F1 hybrid mice, which develop late disease. Detailed analysis of cells from the enlarged lymph nodes and spleens of older MRL/l mice demonstrated that such cells: (a) responded poorly to Con A or allogeneic stimulator cells, even in the presence of exogenous IL-2; (b) did not suppress IL-2 production by normal spleen cells; (c) were relatively incapable of adsorbing or inactivating IL-2; and (d) had a markedly reduced anti-H-2b CTLp frequency in the mesenteric lymph nodes but a normal one in spleen. These results indicate that the proliferating Thy-1.2+, Lyt-1+ T cells in MRL/l mice are defective in their responses to mitogenic stimuli, in IL-2 production, and in expression of acceptor sites for IL-2. The relevance of these defects to the MRL/l disease as well as to the role of IL-2 in autoimmunity in general remains to be determined.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Altman A., Cohen I. R. Cell-free media of mixed lymphocyte cultures augmenting sensitization in vitro of mouse T lymphocytes against allogeneic fibroblasts. Eur J Immunol. 1976 Jul;5(7):437–444. doi: 10.1002/eji.1830050702. [DOI] [PubMed] [Google Scholar]
  2. Bonnard G. D., Yasaka K., Jacobson D. Ligand-activated T cell growth factor-induced proliferation: absorption of T cell growth factor by activated T cells. J Immunol. 1979 Dec;123(6):2704–2708. [PubMed] [Google Scholar]
  3. Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Click R. E., Benck L., Alter B. J. Immune responses in vitro. I. Culture conditions for antibody synthesis. Cell Immunol. 1972 Feb;3(2):264–276. doi: 10.1016/0008-8749(72)90165-7. [DOI] [PubMed] [Google Scholar]
  5. Coutinho A., Larsson E. L., Grönvik K. O., Andersson J. Studies on T lymphocyte activation II. The target cells for concanavalin A-induced growth factors. Eur J Immunol. 1979 Aug;9(8):587–592. doi: 10.1002/eji.1830090803. [DOI] [PubMed] [Google Scholar]
  6. Creighton W. D., Zinkernagel R. M., Dixon F. J. T cell-mediated immune responses of lupus-prone BXSB mice and other murine strains. Clin Exp Immunol. 1979 Aug;37(2):181–189. [PMC free article] [PubMed] [Google Scholar]
  7. Eisenberg R. A., Theofilopoulos A. N., Andrews B. S., Peters C. J., Thor L., Dixon F. J. Natural thymocytotoxic autoantibodies in autoimmune and normal mice. J Immunol. 1979 Jun;122(6):2272–2278. [PubMed] [Google Scholar]
  8. Finke J. H., Orosz C. G., Battisto J. R. Splenic T-killer cells can be generated by allogeneic thymic cells in conjunction with assisting factor. Nature. 1977 May 26;267(5609):353–354. doi: 10.1038/267353a0. [DOI] [PubMed] [Google Scholar]
  9. Gershon R. K., Eardley D. D., Naidorf K., Cantor H. Association of defective feedback suppressor T cell activity with autoimmunity in NZB mice. Arthritis Rheum. 1978 Jun;21(5 Suppl):S180–S184. doi: 10.1002/art.1780210930. [DOI] [PubMed] [Google Scholar]
  10. Gery I., Handschumacher R. E. Potentiation of the T lymphocyte response to mitogens. III. Properties of the mediator(s) from adherent cells. Cell Immunol. 1974 Mar 30;11(1-3):162–169. doi: 10.1016/0008-8749(74)90016-1. [DOI] [PubMed] [Google Scholar]
  11. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  12. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  13. Gillis S., Watson J. Biochemical and biological characterization of lymphocyte regulatory molecules. V. Identification of an interleukin 2-producing human leukemia T cell line. J Exp Med. 1980 Dec 1;152(6):1709–1719. doi: 10.1084/jem.152.6.1709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hodes R. J., Hathcock K. S. In vitro generation of suppressor cell activity: suppression of in vitro induction if cell-mediated cytotoxicity. J Immunol. 1976 Jan;116(1):167–177. [PubMed] [Google Scholar]
  15. Inouye H., Hank J. A., Alter B. J., Bach F. H. TCGF production for cloning and growth of functional human T lymphocytes. Scand J Immunol. 1980;12(2):149–154. doi: 10.1111/j.1365-3083.1980.tb00051.x. [DOI] [PubMed] [Google Scholar]
  16. Lewis D. E., Giorgi J. V., Warner N. L. Flow cytometry analysis of T cells and continuous T-cell lines from autoimmune MRL/l mice. Nature. 1981 Jan 22;289(5795):298–300. doi: 10.1038/289298a0. [DOI] [PubMed] [Google Scholar]
  17. Lindahl K. F., Wilson D. B. Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors. J Exp Med. 1977 Mar 1;145(3):508–522. doi: 10.1084/jem.145.3.508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Peavy D. L., Pierce C. W. Cell-mediated immune responses in vitro. I. Suppression of the generation of cytotoxic lymphocytes by concanavalin A and concanavalin A-activated spleen cells. J Exp Med. 1974 Aug 1;140(2):356–369. doi: 10.1084/jem.140.2.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Plate J. M. Soluble factors substitute for T-T-cell collaboration in generation of T-killer lymphocytes. Nature. 1976 Mar 25;260(5549):329–331. doi: 10.1038/260329a0. [DOI] [PubMed] [Google Scholar]
  20. Revised nomenclature for antigen-nonspecific T cell proliferation and helper factors. J Immunol. 1979 Dec;123(6):2928–2929. [PubMed] [Google Scholar]
  21. Ryser J. E., Cerottini J. C., Brunner K. T. Generation of cytolytic T lymphocytes in vitro. IX. induction of secondary CTL responses in primary long-term MLC by supernatants from secondary MLC. J Immunol. 1978 Feb;120(2):370–377. [PubMed] [Google Scholar]
  22. Ryser J. E., MacDonald H. R. Limiting dilution analysis of alloantigen-reactive T lymphocytes. I. Comparison of precursor frequencies for proliferative and cytolytic responses. J Immunol. 1979 May;122(5):1691–1696. [PubMed] [Google Scholar]
  23. Shaw J., Caplan B., Paetkau V., Pilarski L. M., Delovitch T. L., McKenzie I. F. Cellular origins of co-stimulator (IL2) and its activity in cytotoxic T lymphocyte responses. J Immunol. 1980 May;124(5):2231–2239. [PubMed] [Google Scholar]
  24. Simon M. M., Abenhardt B. Generation of effector cells from T cell subsets. II. Lyt 123 T cells contain the precursors for all primary cytotoxic effector cells and for cells involved in the regulation of cytotoxic responses. Eur J Immunol. 1980 May;10(5):334–341. doi: 10.1002/eji.1830100504. [DOI] [PubMed] [Google Scholar]
  25. Smith K. A., Lachman L. B., Oppenheim J. J., Favata M. F. The functional relationship of the interleukins. J Exp Med. 1980 Jun 1;151(6):1551–1556. doi: 10.1084/jem.151.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Smith K. A. T-cell growth factor. Immunol Rev. 1980;51:337–357. doi: 10.1111/j.1600-065x.1980.tb00327.x. [DOI] [PubMed] [Google Scholar]
  27. Sopori M., Bernstein A., Bach F. H. In vitro sensitization of thymocytes. Role of H-21 I region determinants and cell-free mixed leukocyte culture supernates in generation of cytotoxic responses. J Exp Med. 1978 Oct 1;148(4):953–962. doi: 10.1084/jem.148.4.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stobo J. D., Talal N., Paul W. E. Lymphocyte classes in New Zealand mice. I. Ontogeny and mitogen responsiveness of thymocytes and thymus-derived lymphocytes. J Immunol. 1972 Oct;109(4):692–700. [PubMed] [Google Scholar]
  29. Teh H. S., Harley E., Phillips R. A., Miller R. G. Quantitative studies on the precursors of cytotoxic lymphocytes. I. Characterization of a clonal assay and determination of the size of clones derived from single precursors. J Immunol. 1977 Mar;118(3):1049–1056. [PubMed] [Google Scholar]
  30. Theofilopoulos A. N., Dixon F. J. Etiopathogenesis of murine SLE. Immunol Rev. 1981;55:179–216. doi: 10.1111/j.1600-065x.1981.tb00343.x. [DOI] [PubMed] [Google Scholar]
  31. Theofilopoulos A. N., Eisenberg R. A., Bourdon M., Crowell J. S., Jr, Dixon F. J. Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes. J Exp Med. 1979 Feb 1;149(2):516–534. doi: 10.1084/jem.149.2.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Theofilopoulos A. N., Shawler D. L., Balderas R. S., Elder J. H., Katz D. H., Dixon F. J. Specificities of NZB anti-H-2d CML reactions: role of Qa-1 and retroviral gp70 antigens. J Immunol. 1981 Mar;126(3):1154–1159. [PubMed] [Google Scholar]
  33. Theofilopoulos A. N., Shawler D. L., Katz D. H., Dixon F. J. Patterns of immune reactivity in autoimmune murine strains. I. Cell-mediated immune responses induced by H-2 indentical and H-2 incompatible stimulator cells. J Immunol. 1979 Jun;122(6):2319–2327. [PubMed] [Google Scholar]
  34. Wagner H., Röllinghoff M. T-T-cell interactions during the vitro cytotoxic allograft responses. I. Soluble products from activated Lyl+ T cells trigger autonomously antigen-primed Ly23+ T cells to cell proliferation and cytolytic activity. J Exp Med. 1978 Dec 1;148(6):1523–1538. doi: 10.1084/jem.148.6.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Waksman B. H., Raff M. C., East J. T and B lymphocytes in New Zealand black mice. An analysis of the theta, TL and MBLA markers. Clin Exp Immunol. 1972 May;11(1):1–11. [PMC free article] [PubMed] [Google Scholar]
  36. Watson J., Mochizuki D. Interleukin 2: a class of T cell growth factors. Immunol Rev. 1980;51:257–278. doi: 10.1111/j.1600-065x.1980.tb00324.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES