Literature DB >> 16983067

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

Marianne M Martinic1, Maries F van den Broek, Thomas Rülicke, Christoph Huber, Bernhard Odermatt, Walter Reith, Edit Horvath, Raphael Zellweger, Katja Fink, Mike Recher, Bruno Eschli, Hans Hengartner, Rolf M Zinkernagel.   

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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Year:  2006        PMID: 16983067      PMCID: PMC1599980          DOI: 10.1073/pnas.0606707103

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  40 in total

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