摘要:

The ability of SCID mice to accept xenografts has been exploited to study the survival, function and potential of peripheral blood mononuclear cells (PBMC) from patients with autoimmune disorders to produce tissue injury in the mouse. Studies performed with PBMC obtained from patients with organ specific and multisystem autoimmune diseases indicate that human PBMC survive in SCID mice for several months, produce IgG and autoantibodies with the same specificities as are found in the donor. Tissue injury is not generally observed in the SCID mouse recipient. SCID mice have also been partially reconstituted with bone marrow from BB (diabetic) and MRL (lupus) mice. SCID mice injected with both spleen cells from mice with collagen induced arthritis together with native bovine collagen developed more severe arthritis than the donors. SCID mice have therefore proven to be a useful resource to study autoimmunity. In both xeno- and allografts of mature lymphocytes, graft versus host reactions occur. Further studies will be necessary to improve donor cell survival without aggravating graft versus host disease.

ISSN:0883-0185    

DOI:10.3109/08830189409051175

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Immunological tolerance is the process of inhibiting or eliminating lymphocytes that recognize self-derived antigens. By removing potentially harmful self-reactive clones, this mechanism allows for the random generation of a diverse repertoire of T-cells capable of responding to foreign pathogens. Although all self-reactive T-cells should be removed from the repertoire, it is quite clear from many recent studies that a significant fraction of T-cells bearingγδT-cell receptors (TCR) recognize self-derived antigens in normal healthy mice. The presence of self-reactive T-cells in healthy animals presents a paradox which may be explained by understanding the transient expression of the antigens (e.g., MHC class 1b, Heat Shock Proteins) that have been identified forγδT-cells thus far. Data from experiments with VγI. 1C-γ4 transgenic mice demonstrating the presence of self-reactive 78 T-cells and their influence on lymphoid development and immune surveillance will be examined in this review.

ISSN:0883-0185    

DOI:10.3109/08830189409051176

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189409051177

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Although autoreactive T cells are thought to play a prominent role in autoimmune disease inMRL-lprllprmice, it has been difficult to directly determine if autoreactive T cells escape from the thymus and react with self-antigens in the periphery. Defective expression of the Fas apoptosis antigen inMRL-lpr/lprmice results from the insertion of theETnretrotransposon. The. fas defect can be partially corrected inCD2-fastransgenic mice in which the expressionof fasis corrected in T cells. To identify a possible defect in clonal deletion or clonal anergy induction of auto-specific T cells, we have studiedC51BL/6-lpr/lprtransgenic mice that express TcR genes that recognize a known self-antigen, the male H-Y antigen. In addition, we have analyzed clonal deletion and tolerance induction after neonatal tolerance induction and superantigen-induced arthritis with the class IIMHC reactive superantigen staphylococcal enterotoxin B (SEB) in Vβ38 TcR transgenic and non-transgenicMRL-lpr/lprmice. Neonatal tolerance induction to SEB was normal inIprilprmice. However, over time a loss of tolerance (thymic or peripheral) was observed inIprilprmice but not in+/+TcR transgenic mice. This defect inlpr/lprmice was thymic-dependent and was due to increased CD28/CTLA4 signaling. These results suggest that an apoptosis defect involving both thymocytes and peripheral lymphoid cells leads to autoimmune disease inIprilprmice. The challenge in the future will be to determine the role of defective apoptosis in other autoimmune diseases.

ISSN:0883-0185    

DOI:10.3109/08830189409051178

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189409051174

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor