Th1 memory cells induce lethal allogeneic disease in recipient bone marrow and spleen (169.43)
| Autor: | Joseph Chewning, Weiwei Zhang, Trenton Schoeb, Casey Weaver |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:169.43-169.43 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.186.supp.169.43 |
| Popis: | Graft versus host disease (GVHD) represents a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). We sought to determine if Th1 memory CD4 cells were capable of inducing disease in allogeneic recipients. Studies were performed using the murine MHC Class II-disparate HSCT model, C57BL/6 (B6) to B6.C-H-2bm12 (B6→bm12). Initial studies using naïve CD4 cells in the B6→bm12 model revealed bone marrow aplasia present in diseased mice, in addition to classic GVHD tissue findings. FACS CD4 phenotyping of the transferred cells isolated directly from diseased tissues revealed a marked increase in IFN-γ in the allogeneic mice compared to syngeneic recipients. Using a previously described transgenic Ifng reporter mouse containing the Thy1.1 gene knocked in-frame into the first exon of the Ifng gene, we were able to isolate IFN-γ-producing Th1 cells with magnetic bead separation. Adoptive transfer studies of allogeneic Thy1.1-positive cells into bm12 allogeneic mice resulted in fatality in a dose-dependent fashion. FACS phenotyping of Thy1.1-expressing cells in mice demonstrating illness revealed persistence of the Th1 phenotype and tissue histology showed severe disease of bone marrow and spleen in the absence of classic GVHD findings. Serial blood counts confirmed decreases in all hematologic parameters in allogeneic Th1 recipients. These results have important implications for future studies in graft manipulation for human HSCT. |
| Databáze: | OpenAIRE |
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