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Selection of immature CD4CD8 double-positive (DP) thymocytes for CD4 or CD8-lineage commitment is controlled by the interaction of the TCR with stromal cell-expressed peptide/MHC. We show that thymocyte-intrinsic genes influence the pattern of expression of a MHC class I-restricted transgenic (tg) TCR so that in DBA/2 mice, DP thymocytes with a characteristically high expression of tg TCR, infrequently transit to CD8 single-positive thymocytes. In contrast, in B10.D2 mice, the same tg TCR is expressed at lower levels on a subpopulation of DP thymocytes that more frequently transit to CD8 single-positive thymocytes. These characteristics were not influenced by thymic stromal components that control positive selection. Radiation chimeras reconstituted with a mixture of BM from tg TCR mice of the two genetic backgrounds revealed that the relative frequency of transit to the CD8 lineage remained thymocyte-intrinsic. Identifying the gene products whose polymorphism controls CD8 T cell development may shed new light on the mechanisms controlling T cell commitment/selection in mice other than the most studied "C57BL/6"-based strains.

Type

Journal article

Journal

J Immunol

Publication Date

15/04/2004

Volume

172

Pages

5069 - 5077

Keywords

Animals, Antigens, Neoplasm, Bone Marrow Transplantation, CD3 Complex, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Lineage, Gene Expression Regulation, Hematopoietic Stem Cells, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Organ Specificity, Radiation Chimera, Receptors, Antigen, T-Cell, Stromal Cells, T-Lymphocyte Subsets, Thymus Gland