Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1991 Feb;72(2):219–225.

Unresponsiveness to Mlsa induced in newborn Mlsb mice by maternal preimmunization.

A Matossian-Rogers 1, L DeGiorgi 1, L DeGiori 1
PMCID: PMC1384487  PMID: 1826669

Abstract

Female BALB/c (H-2d, Mlsb) mice alloimmunized prior to and during syngeneic pregnancy with DBA/2 (H-2d, Mlsa) splenocytes gave rise to offspring with severely reduced responsiveness in adult life to DBA/2 stimulation in vitro mixed lymphocyte cultures. The offspring of the hyperimmunized mothers were also tolerant to neonatal challenge with large numbers of DBA/2 splenocytes, which resulted in runting disease of control neonatal BALB/c mice. Both challenged and unchallenged offspring of the immunized BALB/c mothers were hyporesponsive to DBA/2 but both stimulated and responded to normal BALB/c lymphocytes, indicating alteration in their T-cell repertoire. There was no reduction in the V beta 6-positive thymocyte subpopulation in the challenged or unchallenged offspring of the alloimmunized BALB/c mothers compared to normal controls, suggesting that hyporesponsiveness to DBA/2 is not due to thymic deletion of Mlsa-responsive clones. Examination of the T-cell subset composition of the hydrocortisone-resistant thymocytes and peripheral lymphocytes of the challenged and unchallenged groups of experimental mice revealed large increases in the percentage of Lyt-2+ T cells, sometimes accompanied by a decrease in the L3T4+ T-cell subset compared to age-matched control BALB/c. Lymphocytes from the hyporesponsive mice specifically suppressed the proliferative responses of control BALB/c to DBA/2 but not to AKR. The data indicate that maternal hyperimmunization can induce tolerance by a mechanism involving intrathymic selection of suppressor cells which can be combined with a negative selection of helper cells.

Full text

PDF
219

Selected References

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

  1. Abbasi K., Démant P., Festenstein H., Holmes J., Huber B., Rychiková M. Mouse mixed lymphocyte reactions and cell-mediated lympholysis: genetic control and relevance to antigenic strength. Transplant Proc. 1973 Dec;5(4):1329–1337. [PubMed] [Google Scholar]
  2. Abe R., Hodes R. J. T-cell recognition of minor lymphocyte stimulating (Mls) gene products. Annu Rev Immunol. 1989;7:683–708. doi: 10.1146/annurev.iy.07.040189.003343. [DOI] [PubMed] [Google Scholar]
  3. Abe R., Vacchio M. S., Fox B., Hodes R. J. Preferential expression of the T-cell receptor V beta 3 gene by Mlsc reactive T cells. Nature. 1988 Oct 27;335(6193):827–830. doi: 10.1038/335827a0. [DOI] [PubMed] [Google Scholar]
  4. Bandeira A., Coutinho A., Carnaud C., Jacquemart F., Forni L. Transplantation tolerance correlates with high levels of T- and B-lymphocyte activity. Proc Natl Acad Sci U S A. 1989 Jan;86(1):272–276. doi: 10.1073/pnas.86.1.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blackman M. A., Burgert H. G., Gerhard-Burgert H., Woodland D. L., Palmer E., Kappler J. W., Marrack P. A role for clonal inactivation in T cell tolerance to Mls-1a. Nature. 1990 Jun 7;345(6275):540–542. doi: 10.1038/345540a0. [DOI] [PubMed] [Google Scholar]
  6. Bonneville M., Ishida I., Itohara S., Verbeek S., Berns A., Kanagawa O., Haas W., Tonegawa S. Self-tolerance to transgenic gamma delta T cells by intrathymic inactivation. Nature. 1990 Mar 8;344(6262):163–165. doi: 10.1038/344163a0. [DOI] [PubMed] [Google Scholar]
  7. DeGiorgi L., Habeshaw J. A., Povey S., Matossian-Rogers A. Reduction of graft-versus-host disease in neonatal F1 hybrid mice. Clin Exp Immunol. 1990 Jan;79(1):130–134. doi: 10.1111/j.1365-2249.1990.tb05139.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DeGiorgi L., Matossian-Rogers A., Festenstein H. Protection of newborn mice from graft versus host disease by maternal pre-immunization. J Immunogenet. 1990 Feb-Apr;17(1-2):77–88. doi: 10.1111/j.1744-313x.1990.tb00861.x. [DOI] [PubMed] [Google Scholar]
  9. DeGiorgi L., Povey S., Habeshaw J. A., Davies A. J. Prevention of graft-versus-host disease in neonatal F1 hybrid mice by pre-immunisation of their mother with paternal spleen cells. Transplant Proc. 1989 Feb;21(1 Pt 3):3045–3049. [PubMed] [Google Scholar]
  10. Eto M., Mayumi H., Tomita Y., Yoshikai Y., Nomoto K. Intrathymic clonal deletion of V beta 6+ T cells in cyclophosphamide-induced tolerance to H-2-compatible, Mls-disparate antigens. J Exp Med. 1990 Jan 1;171(1):97–113. doi: 10.1084/jem.171.1.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fry A. M., Matis L. A. Self-tolerance alters T-cell receptor expression in an antigen-specific MHC restricted immune response. Nature. 1988 Oct 27;335(6193):830–832. doi: 10.1038/335830a0. [DOI] [PubMed] [Google Scholar]
  12. Haqqi T. M., Banerjee S., Anderson G. D., David C. S. RIII S/J (H-2r). An inbred mouse strain with a massive deletion of T cell receptor V beta genes. J Exp Med. 1989 Jun 1;169(6):1903–1909. doi: 10.1084/jem.169.6.1903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
  14. Kappler J. W., Staerz U., White J., Marrack P. C. Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature. 1988 Mar 3;332(6159):35–40. doi: 10.1038/332035a0. [DOI] [PubMed] [Google Scholar]
  15. Kisielow P., Blüthmann H., Staerz U. D., Steinmetz M., von Boehmer H. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature. 1988 Jun 23;333(6175):742–746. doi: 10.1038/333742a0. [DOI] [PubMed] [Google Scholar]
  16. Kruisbeek A. M., Mond J. J., Fowlkes B. J., Carmen J. A., Bridges S., Longo D. L. Absence of the Lyt-2-,L3T4+ lineage of T cells in mice treated neonatally with anti-I-A correlates with absence of intrathymic I-A-bearing antigen-presenting cell function. J Exp Med. 1985 May 1;161(5):1029–1047. doi: 10.1084/jem.161.5.1029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Liao N. S., Maltzman J., Raulet D. H. Positive selection determines T cell receptor V beta 14 gene usage by CD8+ T cells. J Exp Med. 1989 Jul 1;170(1):135–143. doi: 10.1084/jem.170.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MacDonald H. R., Hengartner H., Pedrazzini T. Intrathymic deletion of self-reactive cells prevented by neonatal anti-CD4 antibody treatment. Nature. 1988 Sep 8;335(6186):174–176. doi: 10.1038/335174a0. [DOI] [PubMed] [Google Scholar]
  19. MacDonald H. R., Lees R. K. Programmed death of autoreactive thymocytes. Nature. 1990 Feb 15;343(6259):642–644. doi: 10.1038/343642a0. [DOI] [PubMed] [Google Scholar]
  20. Marrack P., Lo D., Brinster R., Palmiter R., Burkly L., Flavell R. H., Kappler J. The effect of thymus environment on T cell development and tolerance. Cell. 1988 May 20;53(4):627–634. doi: 10.1016/0092-8674(88)90578-8. [DOI] [PubMed] [Google Scholar]
  21. Maruŝić-Galesić S., Stephany D. A., Longo D. L., Kruisbeek A. M. Development of CD4-CD8+ cytotoxic T cells requires interactions with class I MHC determinants. Nature. 1988 May 12;333(6169):180–183. doi: 10.1038/333180a0. [DOI] [PubMed] [Google Scholar]
  22. Rammensee H. G., Kroschewski R., Frangoulis B. Clonal anergy induced in mature V beta 6+ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells. Nature. 1989 Jun 15;339(6225):541–544. doi: 10.1038/339541a0. [DOI] [PubMed] [Google Scholar]
  23. Roberts J. L., Sharrow S. O., Singer A. Clonal deletion and clonal anergy in the thymus induced by cellular elements with different radiation sensitivities. J Exp Med. 1990 Mar 1;171(3):935–940. doi: 10.1084/jem.171.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schneider R., Lees R. K., Pedrazzini T., Zinkernagel R. M., Hengartner H., MacDonald H. R. Postnatal disappearance of self-reactive (V beta 6+) cells from the thymus of Mlsa mice. Implications for T cell development and autoimmunity. J Exp Med. 1989 Jun 1;169(6):2149–2158. doi: 10.1084/jem.169.6.2149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Speiser D. E., Schneider R., Hengartner H., MacDonald H. R., Zinkernagel R. M. Clonal deletion of self-reactive T cells in irradiation bone marrow chimeras and neonatally tolerant mice. Evidence for intercellular transfer of Mlsa. J Exp Med. 1989 Aug 1;170(2):595–600. doi: 10.1084/jem.170.2.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Webb S. R., Sprent J. Response of mature unprimed CD8+ T cells to Mlsa determinants. J Exp Med. 1990 Mar 1;171(3):953–958. doi: 10.1084/jem.171.3.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zúiga-Pflücker J. C., Jones L. A., Longo D. L., Kruisbeek A. M. CD8 is required during positive selection of CD4-/CD8+ T cells. J Exp Med. 1990 Feb 1;171(2):427–437. doi: 10.1084/jem.171.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES