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Functional CD8+ but not CD4+ T cell responses develop independent of thymic epithelial MHC

Martinic, M. M.
van den Broek, M. F.
Rulicke, Thomas
Huber, Christoph
Odermatt, Bernhard
Horvath, Edit
Zellweger, Raphael
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Published in Proceedings of the National Academy of Sciences. 2006, vol. 103, no. 39, p. 14435-14440
Abstract The role of nonthymic epithelial (non-TE) MHC in T cell repertoire selection remains controversial. To analyze the relative roles of thymic epithelial (TE) and non-TE MHC in T cell repertoire selection, we have generated tetraparental aggregation chimeras (B6-nude<=>BALB/c and B6<=>BALB/c-nude) harboring T and B cells from both parents, whereas TE cells originated exclusively from the non-nude donor. These chimeras mounted protective virus-specific TE and non-TE MHC-restricted T cell responses. To further evaluate whether non-TE MHC alone was sufficient to generate a functional T cell repertoire, we generated tetraparental aggregation chimeras lacking MHC class II (B6-nude<=>MHCII(-/-)) or both MHC molecules (B6-nude<=>MHCI(-/-)II(-/-)) on TE cells, but not on cells of B6-nude origin. Chimeras with MHC-deficient TE cells mounted functional virus-specific CD8+ but not CD4+ T cell responses. Thus, maturation of functional CD4+ T cell responses required MHC class II on thymic epithelium, whereas CD8+ T cells matured in the absence of TE MHC.
Keywords AnimalsB-Lymphocytes/immunologyCD4-Positive T-Lymphocytes/ immunologyCD8-Positive T-Lymphocytes/ immunologyChimera/immunologyEpithelial Cells/ immunologyHistocompatibility Antigens Class II/ immunologyMiceMice, Inbred BALB CMice, Inbred C57BLMice, NudeThymus Gland/ immunologyViruses/immunology
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PMID: 16983067
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