Thymocyte-intrinsic genetic factors influence CD8 T cell lineage commitment and affect selection of a tumor-reactive TCR
(2004) Journal of Immunology — Vol. 172, n° 8, p. 5069-5077 (2004)
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- Abstract
- 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.
- Affiliations
Université de la Méditerranée, Marseille, France Centre d’Immunologie de Marseille-Luminy & CNRS, Institut National de la Santé et de la Recherche Médicale
Citations
Shanker, A., Auphan-Anezin, N., Chomez, P., Giraudo, L., Van den Eynde, B., & Schmitt-Verhulst, A.-M. (2004). Thymocyte-intrinsic genetic factors influence CD8 T cell lineage commitment and affect selection of a tumor-reactive TCR. Journal of Immunology, 172(8), 5069-5077. https://doi.org/10.4049/jimmunol.172.8.5069 (Original work published 2004)