J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/01/357/06 $2.00
Volume 185 January 1997 357-362

BRIEF DEFINITIVE REPORT:
Asynchronous Coreceptor Downregulation after Positive Thymic Selection: Prolonged Maintenance of the Double Positive State in CD8 Lineage Differentiation Due to Sustained Biosynthesis of the CD4 Coreceptor

By Thomas Barthlott, Hubertus Kohler, and Klaus Eichmann

From the Max-Planck-Institut für Immunbiologie, Stübeweg 51, 79108 Freiburg, Germany

In several experimental systems analyzing the generation of single positive (SP) thymocytes from double positive (DP) thymocytes, CD4 SP cells have been shown to appear before CD8 SP cells. This apparent temporal asymmetry in the maturation of CD4 SP and CD8 SP thymocytes could either be due to divergent molecular differentiation programs of the two T cell lineages, or merely to slower degradation kinetics of the CD4 protein. To study this question in unmanipulated in vivo differentiation, we developed a four-color flow cytometry protocol which identifies a recently activated TCR^intCD69^pos thymocyte population containing DP cells and early CD4 SP cells but no CD8 SP cells. We show that these TCR^intCD69^pos thymocytes represent a transitory stage in the mainstream T cell lineage. The precursors of the CD8 SP cells are contained in this population as incompletely selected DP cells. Moreover, we show that expression of both coreceptors in the TCR^intCD69^pos population depends on transcriptional and translational activity, thus excluding differences in turnover rates of the CD4 and CD8 proteins as the cause of the asynchrony in differentiation of the CD4 and CD8 lineages.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Eshima, K., Suzuki, H., Shinohara, N. (2006). Cross-Positive Selection of Thymocytes Expressing a Single TCR by Multiple Major Histocompatibility Complex Molecules of Both Classes: Implications for CD4+ versus CD8+ Lineage Commitment. J. Immunol. 176: 1628-1636 [Abstract] [Full Text]  
• Liu, X., Taylor, B. J., Sun, G., Bosselut, R. (2005). Analyzing Expression of Perforin, Runx3, and Thpok Genes during Positive Selection Reveals Activation of CD8-Differentiation Programs by MHC II-Signaled Thymocytes. J. Immunol. 175: 4465-4474 [Abstract] [Full Text]  
• Delaire, S., Huang, Y. H., Chan, S. W., Robey, E. A. (2004). Dynamic Repositioning of CD4 and CD8 Genes during T Cell Development. JEM 200: 1427-1435 [Abstract] [Full Text]  
• Yucel, R., Kosan, C., Heyd, F., Moroy, T. (2004). Gfi1:Green Fluorescent Protein Knock-in Mutant Reveals Differential Expression and Autoregulation of the Growth Factor Independence 1 (Gfi1) Gene during Lymphocyte Development. J. Biol. Chem. 279: 40906-40917 [Abstract] [Full Text]  
• Ehlers, M., Laule-Kilian, K., Petter, M., Aldrian, C. J., Grueter, B., Wurch, A., Yoshida, N., Watanabe, T., Satake, M., Steimle, V. (2003). Morpholino Antisense Oligonucleotide-Mediated Gene Knockdown During Thymocyte Development Reveals Role for Runx3 Transcription Factor in CD4 Silencing During Development of CD4-/CD8+ Thymocytes. J. Immunol. 171: 3594-3604 [Abstract] [Full Text]  
• Bosselut, R., Guinter, T. I., Sharrow, S. O., Singer, A. (2003). Unraveling a Revealing Paradox: Why Major Histocompatibility Complex I-signaled Thymocytes "Paradoxically" Appear as CD4+8lo Transitional Cells During Positive Selection of CD8+ T Cells. JEM 197: 1709-1719 [Abstract] [Full Text]  
• Yucel, R., Karsunky, H., Klein-Hitpass, L., Moroy, T. (2003). The Transcriptional Repressor Gfi1 Affects Development of Early, Uncommitted c-Kit+ T Cell Progenitors and CD4/CD8 Lineage Decision in the Thymus. JEM 197: 831-844 [Abstract] [Full Text]  
• Cho, H. J., Edmondson, S. G., Miller, A. D., Sellars, M., Alexander, S. T., Somersan, S., Punt, J. A. (2003). Cutting Edge: Identification of the Targets of Clonal Deletion in an Unmanipulated Thymus. J. Immunol. 170: 10-13 [Abstract] [Full Text]  
• Puls, K. L., Hogquist, K. A., Reilly, N., Wright, M. D. (2002). CD53, a thymocyte selection marker whose induction requires a lower affinity TCR-MHC interaction than CD69, but is up-regulated with slower kinetics. Int Immunol 14: 249-258 [Abstract] [Full Text]  
• Lauzurica, P., Sancho, D., Torres, M., Albella, B., Marazuela, M., Merino, T., Bueren, J. A., Martinez-A, C., Sanchez-Madrid, F. (2000). Phenotypic and functional characteristics of hematopoietic cell lineages in CD69-deficient mice. Blood 95: 2312-2320 [Abstract] [Full Text]  
• Wurch, A., Biro, J., Potocnik, A. J., Falk, I., Mossmann, H., Eichmann, K. (1998). Requirement of CD3 Complex-associated Signaling Functions for Expression of Rearranged T Cell Receptor beta  VDJ Genes in Early Thymic Development. JEM 188: 1669-1678 [Abstract] [Full Text]  
• Hare, K. J., Wilkinson, R. W., Jenkinson, E. J., Anderson, G. (1998). Identification of a Developmentally Regulated Phase of Postselection Expansion Driven by Thymic Epithelium. J. Immunol. 160: 3666-3672 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS