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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Adoptive Transfer, Animals, CD4 Antigens, CD8 Antigens, Graft Survival, Isoantigens, Lymphocyte Depletion, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Transgenic, Skin Transplantation, Spleen.
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Does donor-specific antigen transfusion-mediated skin-graft tolerance result from the peripheral deletion of donor-reactive CD8+ T cells? Context: The mechanism of donor-specific transfusion (DST)-induced long-term skin-graft survival is examined in 2CF1 (2C x dm2) transgenic and B6F1 (C57BL/6 x dm2) nontransgenic mice in which CB6F1 (Balb/c x B6) DST and donor skin grafts differ from 2CF1 or B6F1 recipients only at major histocompatibility complex class I Ld. Saline (control) or allogeneic CB6F1 spleen cells were injected intravenously into 2CF1 and B6F1 mice. One week later, CB6F1 tail skin was transplanted onto the dorsum of these mice. Fluorescence-activated cell sorter analysis (flow cytometric analysis) of peripheral blood was performed 2 days before DST, 5 days after DST, and 7, 14, 21, 28, and 75 days after skin grafting. Splenocyte responsiveness was measured by in vitro mixed lymphocyte culture and cytotoxic T lymphocyte. Cytokine protein production (interleukin [IL]-2 and interferon-gamma) was measured by enzyme-linked immunosorbent assay. Whereas all CB6F1 skin grafts in control saline-treated 2CF1 and B6F1 mice were rejected, 100% of 2CF1 and B6F1 pretreated with CB6F1 DST accepted the class I Ld disparate donor skin indefinitely. DST followed by a CB6F1 skin graft led to a significant deletion of donor-reactive CD8+ T cells by fluorescence-activated cell sorter analysis and decreased production of the inflammatory cytokines IL-2 and interferon-gamma. The hyporesponsiveness of residual CD8+ T cells in mixed lymphocyte culture and cytotoxic T lymphocyte to Ld after DST was restored to normal by IL-2.
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These findings demonstrate that administration of DST uniformly results in long-term Ld+ skin-allograft acceptance. This tolerance induction is related to both a significant decrease in donor-reactive CD8+ transgenic T cells and anergy of the residual CD8+ T cells. Final Decision: yes