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Brief Definitive Report |
honjo{at}mfour.med.kyoto-u.ac.jp
PD-1 is an immunoglobulin superfamily member bearing an immunoreceptor tyrosine-based inhibitory motif, and disruption of the PD-1 gene results in the development of lupus-like autoimmune diseases. In this study, we examined effects of the PD-1 deficiency on the thymocyte differentiation at the clonal level using T cell receptor (TCR)-β (Vβ8) and TCR-
/β (H-Y and 2C) transgenic mice. In these TCR transgenic lines, PD-1 expression in the thymus was variably augmented, but as in the normal mice, confined largely to the CD4–CD8– thymocytes. The transgenic mice crossed with PD-1–/– mice in the neutral genetic backgrounds exhibited selective increase in the CD4+CD8+ (DP) population with little effect on other thymocytes subsets. Similarly, the absence of PD-1 facilitated expansion of DP thymocytes in recombination activating gene (RAG)-2–/– mice by anti-CD3
antibody injection. On the other hand, H-Y or 2C transgenic PD-1–/– mice with the positively selecting background showed significantly reduced efficiency for the generation of CD8+ single positive cells bearing the transgenic TCR-/β in spite of the increased DP population. These results collectively indicate that PD-1 negatively regulates the β selection and modulates the positive selection, and suggest that PD-1 deficiency may lead to the significant alteration of mature T cell repertoire.
Key Words: immunoreceptor tyrosine-based inhibitory motif • knock-out mice • positive selection • T cell receptor transgenic mice • RAG-2–deficient mice
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