Skip to main content
Immunology logoLink to Immunology
. 1995 Oct;86(2):162–167.

Oestrogen influences CD4+ T-lymphocyte activity in vivo and in vitro in beta 2-microglobulin-deficient mice.

D Muller 1, M Chen 1, A Vikingsson 1, D Hildeman 1, K Pederson 1
PMCID: PMC1383990  PMID: 7490113

Abstract

Oestrogen directly influences autoimmune diseases and the immune response to microbes. We studied the effect of oestrogen on CD4+ T cells specific for lymphocytic choriomeningitis virus (LCMV) using mice genetically engineered to be deficient in beta 2-microglobulin (beta 2m-/-). These mice are deficient in beta 2-microglobulin, class I major histocompatibility complex (MHC) molecules and CD8+ T lymphocytes. Fatal leptomeningitis after intracranial infection with LCMV is mediated by CD8+ cytotoxic T lymphocytes (CTL) in wild-type C57BL/6 mice, and by CD4+ T cells in beta 2m-/- mice. Male and female wild-type C57BL/6 mice showed equal susceptibility to immune meningitis. In contrast, male beta 2m-/- mice were less susceptible to fatal immune meningitis than were females. Orchidectomy and oestrogen treatment of male beta 2m-/- mice in vivo restored susceptibility to meningitis. The classic weight loss seen in beta 2m-/- mice after intracranial infection was also accentuated in females. Further, the in vitro activity of CD4+ T cells from male beta 2m-/- mice, as measured by CTL assays, was shown to be dependent on oestrogen. The natural killer cell activity of spleen cells from beta 2m-/- mice after infection with LCMV was not affected by oestrogen. These data demonstrate the influence of oestrogen on CD4+ T-cell activity both in vivo and in vitro.

Full text

PDF
162

Selected References

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

  1. Apasov S., Sitkovsky M. Highly lytic CD8+, alpha beta T-cell receptor cytotoxic T cells with major histocompatibility complex (MHC) class I antigen-directed cytotoxicity in beta 2-microglobulin, MHC class I-deficient mice. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2837–2841. doi: 10.1073/pnas.90.7.2837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Best G. K., Abney T. O., Kling J. M., Kirkland J. J., Scott D. F. Hormonal influence on experimental infections by a toxic shock strain of Staphylococcus aureus. Infect Immun. 1986 Apr;52(1):331–333. doi: 10.1128/iai.52.1.331-333.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Browning M. J., Huang A. S., Reiss C. S. Cytolytic T lymphocytes from the BALB/c-H-2dm2 mouse recognize the vesicular stomatitis virus glycoprotein and are restricted by class II MHC antigens. J Immunol. 1990 Aug 1;145(3):985–994. [PubMed] [Google Scholar]
  4. Cutolo M., Balleari E., Giusti M., Intra E., Accardo S. Androgen replacement therapy in male patients with rheumatoid arthritis. Arthritis Rheum. 1991 Jan;34(1):1–5. doi: 10.1002/art.1780340102. [DOI] [PubMed] [Google Scholar]
  5. Dalton D. K., Pitts-Meek S., Keshav S., Figari I. S., Bradley A., Stewart T. A. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science. 1993 Mar 19;259(5102):1739–1742. doi: 10.1126/science.8456300. [DOI] [PubMed] [Google Scholar]
  6. Fox H. S., Bond B. L., Parslow T. G. Estrogen regulates the IFN-gamma promoter. J Immunol. 1991 Jun 15;146(12):4362–4367. [PubMed] [Google Scholar]
  7. Grossman C. J. Interactions between the gonadal steroids and the immune system. Science. 1985 Jan 18;227(4684):257–261. doi: 10.1126/science.3871252. [DOI] [PubMed] [Google Scholar]
  8. Homo-Delarche F., Fitzpatrick F., Christeff N., Nunez E. A., Bach J. F., Dardenne M. Sex steroids, glucocorticoids, stress and autoimmunity. J Steroid Biochem Mol Biol. 1991;40(4-6):619–637. doi: 10.1016/0960-0760(91)90285-d. [DOI] [PubMed] [Google Scholar]
  9. Hou S., Doherty P. C., Zijlstra M., Jaenisch R., Katz J. M. Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T cells. J Immunol. 1992 Aug 15;149(4):1319–1325. [PubMed] [Google Scholar]
  10. Huang S., Hendriks W., Althage A., Hemmi S., Bluethmann H., Kamijo R., Vilcek J., Zinkernagel R. M., Aguet M. Immune response in mice that lack the interferon-gamma receptor. Science. 1993 Mar 19;259(5102):1742–1745. doi: 10.1126/science.8456301. [DOI] [PubMed] [Google Scholar]
  11. Jansson L., Holmdahl R. Oestrogen-induced suppression of collagen arthritis; 17 beta-oestradiol is therapeutically active in normal and castrated F1 hybrid mice of both sexes. Clin Exp Immunol. 1992 Sep;89(3):446–451. doi: 10.1111/j.1365-2249.1992.tb06978.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kolaitis G., Doymaz M., Rouse B. T. Demonstration of MHC class II-restricted cytotoxic T lymphocytes in mice against herpes simplex virus. Immunology. 1990 Sep;71(1):101–106. [PMC free article] [PubMed] [Google Scholar]
  13. Koller B. H., Marrack P., Kappler J. W., Smithies O. Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science. 1990 Jun 8;248(4960):1227–1230. doi: 10.1126/science.2112266. [DOI] [PubMed] [Google Scholar]
  14. Lanzavecchia A. Is suppression a function of class II--restricted cytotoxic T cells? Immunol Today. 1989 May;10(5):157–159. doi: 10.1016/0167-5699(89)90172-2. [DOI] [PubMed] [Google Scholar]
  15. Leist T. P., Eppler M., Zinkernagel R. M. Enhanced virus replication and inhibition of lymphocytic choriomeningitis virus disease in anti-gamma interferon-treated mice. J Virol. 1989 Jun;63(6):2813–2819. doi: 10.1128/jvi.63.6.2813-2819.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Littaua R. A., Oldstone M. B., Takeda A., Ennis F. A. A CD4+ cytotoxic T-lymphocyte clone to a conserved epitope on human immunodeficiency virus type 1 p24: cytotoxic activity and secretion of interleukin-2 and interleukin-6. J Virol. 1992 Jan;66(1):608–611. doi: 10.1128/jvi.66.1.608-611.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Loria R. M., Inge T. H., Cook S. S., Szakal A. K., Regelson W. Protection against acute lethal viral infections with the native steroid dehydroepiandrosterone (DHEA). J Med Virol. 1988 Nov;26(3):301–314. doi: 10.1002/jmv.1890260310. [DOI] [PubMed] [Google Scholar]
  18. Muller D., Koller B. H., Whitton J. L., LaPan K. E., Brigman K. K., Frelinger J. A. LCMV-specific, class II-restricted cytotoxic T cells in beta 2-microglobulin-deficient mice. Science. 1992 Mar 20;255(5051):1576–1578. doi: 10.1126/science.1347959. [DOI] [PubMed] [Google Scholar]
  19. Okuyama R., Abo T., Seki S., Ohteki T., Sugiura K., Kusumi A., Kumagai K. Estrogen administration activates extrathymic T cell differentiation in the liver. J Exp Med. 1992 Mar 1;175(3):661–669. doi: 10.1084/jem.175.3.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Quinn D. G., Zajac A. J., Frelinger J. A., Muller D. Transfer of lymphocytic choriomeningitis disease in beta 2-microglobulin-deficient mice by CD4+ T cells. Int Immunol. 1993 Oct;5(10):1193–1198. doi: 10.1093/intimm/5.10.1193. [DOI] [PubMed] [Google Scholar]
  21. Raveche E. S., Tjio J. H., Steinberg A. D. Genetic studies in NZB mice. III. Induced anti-nucleic acid antibody production. J Immunol. 1979 Apr;122(4):1454–1460. [PubMed] [Google Scholar]
  22. Roubinian J. R., Talal N., Greenspan J. S., Goodman J. R., Siiteri P. K. Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice. J Exp Med. 1978 Jun 1;147(6):1568–1583. doi: 10.1084/jem.147.6.1568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Spriggs M. K., Koller B. H., Sato T., Morrissey P. J., Fanslow W. C., Smithies O., Voice R. F., Widmer M. B., Maliszewski C. R. Beta 2-microglobulin-, CD8+ T-cell-deficient mice survive inoculation with high doses of vaccinia virus and exhibit altered IgG responses. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6070–6074. doi: 10.1073/pnas.89.13.6070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sthoeger Z. M., Chiorazzi N., Lahita R. G. Regulation of the immune response by sex hormones. I. In vitro effects of estradiol and testosterone on pokeweed mitogen-induced human B cell differentiation. J Immunol. 1988 Jul 1;141(1):91–98. [PubMed] [Google Scholar]
  25. Styrt B., Sugarman B. Estrogens and infection. Rev Infect Dis. 1991 Nov-Dec;13(6):1139–1150. doi: 10.1093/clinids/13.6.1139. [DOI] [PubMed] [Google Scholar]
  26. Tarleton R. L., Koller B. H., Latour A., Postan M. Susceptibility of beta 2-microglobulin-deficient mice to Trypanosoma cruzi infection. Nature. 1992 Mar 26;356(6367):338–340. doi: 10.1038/356338a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES