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1990 Fiscal Year Final Research Report Summary

Role of T Cells (Thymus) in H-2-Linked Control of Autoimmune Disease

Research Project

Project/Area Number 01570269
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionOsaka University Medical School

Principal Investigator

ONO Shiro  Osaka University Medical School, Lecturer, 医学部, 講師 (80127208)

Project Period (FY) 1989 – 1990
KeywordsAutoimmune disease / H-2-linked control / (NZBxNZW)F1 mice / Thymus graft / Radiation-induced bone marrow chimera / T-cell repertoire
Research Abstract

The development of human systemic lupus erythematosus (SLE) -like disease in (NZB x NZW) F1 (BWF1, H-2^<d/z>) mice was thought to be resulted primarily from their hyper-reactivity of B cell-function. However, We have demonstrated recently that congenitally athymic BWF1 nude mice fail to develop the disease, and that the engrafting thymus from BWF1 mice into BWF1 nude mice manifest the SLE-like disease. These results indicate the obligatory requirement fot thymus (T cells) in the development of autoimmune disease in BWF1 mice. Although it has been shown that H-2 gene products NZW mice play a crucial role in the onset of autoimmune disease in BWF1 mice, the mechanisms underlying the H-2-linked control are not clear at present.
This study was undertaken to investigate the possible association of thymic genotype with autoimmune manifestations in BWF1 mice by utilizing BWF1 nude mice engrafted with NZB (H-2^d), NZW (H-2^z), or BWF1 thymus. The development of SLE-like disease characterized by spontaneous product
ion of anti-ssDNA IgG antibodies and appearance of proteinuria was retarded in BWF1 nude mice engrafted with NZB thymus as compared to those engrafted with NZW or BWF1 mice, suggesting a crucial role of thymic H-2 genotype the disease. Moreover, T cells derived from lethally irradiated NZW or BWF1 mice reconstituted with BWF1 bone marrow cells ( BWF1->NZW or BWF1->BWF1 chimeras ) exhibited high helper activities capable of inducing in vitro anti-ssDNA IgG antibodies, while such a helper activity was not detected in T cells from BWF1->NZB chimeras.
The present results support the notion that the H-2-linked control of autoimmune disease in BWF1 mice is attributable to the influence of H-2 genotype of thymus on the generation of helper T cells responsible for auto-antibody production of IgG class.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Y.Takahama et al.: "Cluster fomation among small resting B lymphocytes leading to B cell activation" International Immunology. 1. 36-42 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Takahama et al.: "Disparate functions of IーA and IーE molecules on B cells as evidenced by the inhibition with antiーIーA and antiーIーE antibodies of polyclonal B cell activation" Eur.J.Immunol.19. 2227-2235 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Ishihara et sl.: "Different effect of prostaglandin E2 on Bーcell activation by two distinct Bーcell differentiation factors, B151ーTRF1/ILー5 and B151ーTRF2:Selective inhibition of B151ーTRF2ーinducued antiboay response through increases in intracellular cyclic AMP levils" Immunol.68. 154-162 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Seki et al.: "Type II collagenーinduced murine arthritis II. Genetic control of arthritis induction is expressed on L3T4^+ T cells reguired for humoral as well as cellーmediated immune response to type II collagen" Regional Immunol.2. 203-212 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Takahama et al.: "BーB cell interaction involved in polyclonal B cell activation is restricted by IーA moleunles but not by IーE molecules" International Immunology. 2. 63-71 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Miyake et al.: "Monoclonal antibodies to Pgp^<-1>/CD44 block lymphoーhemopoiesis in long term bone marrow cultures" J.Exp.Med.171. 477-488 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y. Takahama et al.: "Cluster formation among small resting B lymphocytes leading to B cell activation" Int. Immunol.1. 36-42 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Hamaoka et al.: "I-A-restricted B-B cell interaction : Obligatory role of B-lineage educator cells in the acquisition of self-recognition specificity" FASEB J.3. A673 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Takahama et al.: "Disparate functions of I-A and I-E molecules on B cells as evidenced by the inhibition with anti-I-A and anti-I-E antibodies of polyclonal B cell activation" Eur. J. Immunol.19. 2227-2235 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Ishihara et al: "Different effect of prostaglandin E2 on B-cell activation by two distinct B-cell differentiation factors, B151-TRF1/IL-5 and B151-TRF2 : selective inhibition of B151-TRF2-induced antibody response through increases in intracellular cyclic AMP levels" Immunol. 68. 154-162 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N. Seki et al: "Type II collagen-induced murine arthritis. II Genetic control of arthritis induction is expressed on L3T4^+ T cells required for humoral as well as cell-mediated immune response to type II collagen." Regional. Immunol.2. 203-212 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Takahama et al.: "Involvement of I-A-restricted B-B cell interaction in the polyclonal B cell differentiation induced by lipopolysaccharide" Advances in Experimental Medicine and Biology. 256. 427-443 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Takahama et al.: "B-B cell interaction involved in polyclonal B cell activation is restricted by I-A molecule but not by I-E molecule" Int. Immunol.2. 63-71 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Miyake et al.: "Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long term bone marrow cultures" J. Exp. Med.171. 477-488 (1990)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-08-12  

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