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  • Title: Functional CD8+ but not CD4+ T cell responses develop independent of thymic epithelial MHC.
    Author: Martinic MM, van den Broek MF, Rülicke T, Huber C, Odermatt B, Reith W, Horvath E, Zellweger R, Fink K, Recher M, Eschli B, Hengartner H, Zinkernagel RM.
    Journal: Proc Natl Acad Sci U S A; 2006 Sep 26; 103(39):14435-40. PubMed ID: 16983067.
    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.
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