Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.
Xenogeneic iso-skin graft and mixed lymphocyte reaction studies using HLA-DP transgenic mice.
Transpl Immunol. 1996 Sep;4(3):220-6. Unique Identifier : AIDSLINE MED/97048622 Hagihara M; Shimura T; Takebe K; Munkhbat B; Sato T; Tsuchida F; Sato K; Tsuji K; Department of Transplantation Immunology, Tokai University School; of Medicine, Kanagawa, Japan.
Abstract:
To elucidate the cellular responses against xeno-MHC antigens, in vitro mixed lymphocyte culture (MLC) and in vivo skin grafting (SG) studies were conducted using HLA-DP transgenic mice (B6-DP mice). Xenogenic iso-(B6-DP to B6 mice) MLC showed positive but much lower responses compared to allo-MLC responses. Nevertheless, B6-DP skin grafts were rejected in a similar time course as allo-skin grafts. To examine mechanisms underlining skin graft rejection, both in vitro cytotoxic lymphocyte (CTL) responses and delayed-type hypersensitivity (DTH) reactions were tested. The studies showed that DTH but not CTL reactions were involved for the graft rejection. SG was again conducted after the administration of anti-CD4 and/or CD8 monoclonal antibody (mAb). Mice treated with both CD4 and CD8 mAb accepted B6-DP SG for as long as up to 60 days and those treated with either CD4 or CD8 mAb alone rejected skin grafts on its own most of the time (75% in anti-CD4 mAb treated mice, 88.9% in anti-CD8 mAb treated mice), which suggests that the strict T cell restrictions for xeno-DP antigens do not exist. Even in these finally rejected cases, longer median survival time and final rejection time were observed, and in the other mice (25% in anti-CD4 mAb treated, and 11.1% in anti-CD8 mAb treated mice), graft acceptance was found. Therefore, it was suggested that the immunological reactions leading to the graft rejection occurs most efficiently when both T cell subsets are present. The above results indicate that xenogeneic HLA-DP antigens could act as significant transplantation antigens equivalent to alloantigens despite their lower stimulative activity in vitro, and also support the interpretation that DP antigens act like a minor histocompatibility antigen beyond the difference of species. Monomorphic anti-HLA class II antibodies were detected in recipients' sera as early as 2 weeks and even at 6 months, indicating that xeno-MHC antigens are prone to be memorized to B cells. It was concluded that HLA transgenic mice are useful for the investigation of cellular responses across xeno-MHC barriers.
Keywords: Animal Antibodies/ANALYSIS CD4-CD8 Ratio Histocompatibility Antigens Class II/IMMUNOLOGY Hypersensitivity, Delayed/IMMUNOLOGY HLA-DP Antigens *Lymphocyte Culture Test, Mixed Lymphocyte Transformation Lymphocytes/IMMUNOLOGY Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Transgenic/*IMMUNOLOGY Skin/IMMUNOLOGY Skin Transplantation/*IMMUNOLOGY/PATHOLOGY Spleen/CYTOLOGY T-Lymphocytes, Cytotoxic/IMMUNOLOGY Transplantation, Heterologous Transplantation, Isogeneic JOURNAL ARTICLE 970228
M9721933
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Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.
