In allogeneic transplantation, including the B6 anti-BALB.B settings, H60 and H4 are two representative dominant minor histocompatibility antigens that induce strong CD8 T-cell responses. With different distribution patterns, H60 expression is restricted to hematopoietic cells, whereas H4 is ubiquitously expressed. H60-specific CD8 T-cell response has been known to be dominant in most cases of B6 anti-BALB.B allo-responses, except in the case of skin transplantation. To understand the mechanism underlying the subdominance of H60 during allogeneic skin transplantation, we investigated the dynamics of the H60-specific CD8 T cells in B6 mice transplanted with allogeneic BALB.B tail skin. Unexpectedly, longitudinal bioluminescence imaging and flow cytometric analyses revealed that H60-specific CD8 T cells were not always subdominant to H4-specific cells but instead showed a brief dominance before the H4 response became predominant. H60-specific CD8 T cells could expand in the draining lymph node and migrate to the BALB.B allografts, indicating their active participation in the anti-BALB.B allo-response. Enhancing the frequencies of H60-reactive CD8 T cells prior to skin transplantation reversed the immune hierarchy between H60 and H4. Additionally, H60 became predominant when antigen presentation was limited to the direct pathway. However, when antigen presentation was restricted to the indirect pathway, the expansion of H60-specific CD8 T cells was limited, whereas H4-specific CD8 T cells expanded significantly, suggesting that the temporary immunodominance and eventual subdominance of H60 could be due to their reliance on the direct antigen presentation pathway. These results enhance our understanding of the immunodominance phenomenon following allogeneic tissue transplantation.
Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology/metabolism ; CD8-Positive T-Lymphocytes/*immunology ; Epitopes, T-Lymphocyte/*immunology ; Female ; Graft Rejection/*immunology ; Interferon-gamma ; Lymphocyte Activation/immunology ; Lymphocyte Count ; Mice ; Minor Histocompatibility Antigens/*immunology/metabolism ; *Skin Transplantation ; Transplantation, Homologous

OBJECTIVETo explore the role of lung interstitial dendritic cells in immunodissonance and organ injury in multiple organ dysfunction syndrome (MODS).

METHODSAnimal model of MODS was established by injecting zymosan into the peritoneal cavity of C57BL/6 mice. The mice were randomly divided into groups of normal, 3 - 6 hours, 12 - 48 hours, 5 - 7 days, 10 - 12 days post injection. Pathological changes of lung and interstitial dendritic cells were studied by light and transmission electron microscope. Immunohistochemistry, RT-PCR and flow cytometry analyses were used to document status of biomarkers, including specific surface markers (CD205 and CD11c), costimulatory molecules (CD80 and CD86), SLC and its receptor CCR7 in lung, CD4+ and CD8+ T lymphocyte subtypes in peripheral blood.

RESULTSAt early stage of injury, interstitial dendritic cells showed an increase in proliferation with expression of low level of CD80 and CD86. In contrast, the expression of SLC and its receptor CCR7 in lung were increased. The ratio of CD4+/CD8+ declined in peripheral blood. At the stage of SIRS, interstitial dendritic cells continued to proliferate with high expressions of CD80 and CD86. SLC and CCR7 in lung also increased. The ratio of CD4+/CD8+ declined markedly in peripheral blood. At the MODS stage, interstitial dendritic cells further proliferated, but the expression of CD80 and CD86 declined to a very low level. Although the level of SLC increased consistently, the level of CCR7 continued to decrease, along with a markedly decreased CD4+/CD8+ ratio in peripheral blood.

CONCLUSIONSAlterations of lung interstitial dendritic cells are likely to influence the course of immunological dysfunction of MODS. The level of CCR7 may serve as an indicator of the migration activity of interstitial dendritic cells and systemic immune response.

Animals ; Antigens, CD ; metabolism ; B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; CD11c Antigen ; metabolism ; CD4-CD8 Ratio ; Cell Proliferation ; Chemokine CCL21 ; metabolism ; Dendritic Cells ; immunology ; metabolism ; ultrastructure ; Disease Models, Animal ; Lectins, C-Type ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Minor Histocompatibility Antigens ; Multiple Organ Failure ; chemically induced ; immunology ; metabolism ; pathology ; Random Allocation ; Receptors, CCR7 ; metabolism ; Receptors, Cell Surface ; metabolism ; Zymosan