HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, X. Articles by Bosselut, R. Search for Related Content PubMed PubMed Citation Articles by Liu, X. Articles by Bosselut, R.

Analyzing Expression of Perforin, Runx3, and Thpok Genes during Positive Selection Reveals Activation of CD8-Differentiation Programs by MHC II-Signaled Thymocytes

Xiaolong Liu^*,, Barbara J. Taylor, Guangping Sun^* and Rémy Bosselut^1,*

^* Laboratory of Immune Cell Biology and FACS Core, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

Intrathymic positive selection matches CD4-CD8 lineage differentiation to MHC specificity. However, it is unclear whether MHC signals induce lineage choice or simply select thymocytes of the appropriate lineage. To investigate this issue, we assessed thymocytes undergoing positive selection for expression of the CD8 lineage markers perforin and Runx3. Using both population-based and single-cell RT-PCR analyses, we found large subsets of MHC class II (MHC-II)-signaled thymocytes expressing these genes within the CD4⁺8⁺ and CD4⁺8^int, but not the CD4⁺8^– populations of signaling competent mice. This indicates that MHC-II signals normally fail to impose CD4 differentiation and further implies that the number of mature CD8 single-positive (SP) thymocytes greatly underestimates CD8 lineage choice. We next examined whether MHC-II-restricted CD4⁺8^– thymocytes remain competent to initiate CD8 lineage gene expression. In mice in which expression of the tyrosine kinase Zap70 and thereby TCR signaling were impaired selectively in SP thymocytes, MHC-II-signaled CD4⁺8^– thymocytes expressed perforin and Runx3 and failed to up-regulate the CD4 marker Thpok. This indicated that impairing TCR signals at the CD4 SP stage switched gene expression patterns from CD4- to CD8-lineage specific. We conclude from these findings that MHC-II-signaled thymocytes remain competent to initiate CD8-specific gene expression even after CD8 down-regulation and that CD4 lineage differentiation is not fixed before the CD4 SP stage.

This article has been cited by other articles:

				S. Van Coppernolle, G. Verstichel, F. Timmermans, I. Velghe, D. Vermijlen, M. De Smedt, G. Leclercq, J. Plum, T. Taghon, B. Vandekerckhove, et al. Functionally Mature CD4 and CD8 TCR{alpha}{beta} Cells Are Generated in OP9-DL1 Cultures from Human CD34+ Hematopoietic Cells J. Immunol., October 15, 2009; 183(8): 4859 - 4870. [Abstract] [Full Text] [PDF]

				K. Kakugawa, T. Yasuda, I. Miura, A. Kobayashi, H. Fukiage, R. Satoh, M. Matsuda, H. Koseki, S. Wakana, H. Kawamoto, et al. A Novel Gene Essential for the Development of Single Positive Thymocytes Mol. Cell. Biol., September 15, 2009; 29(18): 5128 - 5135. [Abstract] [Full Text] [PDF]

				F. Cruz-Guilloty, M. E. Pipkin, I. M. Djuretic, D. Levanon, J. Lotem, M. G. Lichtenheld, Y. Groner, and A. Rao Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs J. Exp. Med., January 16, 2009; 206(1): 51 - 59. [Abstract] [Full Text] [PDF]

				K. F. Wildt, G. Sun, B. Grueter, M. Fischer, M. Zamisch, M. Ehlers, and R. Bosselut The Transcription Factor Zbtb7b Promotes CD4 Expression by Antagonizing Runx-Mediated Activation of the CD4 Silencer J. Immunol., October 1, 2007; 179(7): 4405 - 4414. [Abstract] [Full Text] [PDF]