J. Exp. Med.
© The Rockefeller University Press
0022-1007/96/12/2091/10 $2.00
Volume 184 December 1996 2091-2100

Lineage Commitment in the Thymus: Only the Most Differentiated (TCR^hibcl-2^hi) Subset of CD4⁺CD8⁺ Thymocytes Has Selectively Terminated CD4 or CD8 Synthesis

By Jennifer A. Punt, Harumi Suzuki, Larry G. Granger, Susan O. Sharrow, and Alfred Singer

From the Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Lineage commitment is a developmental process by which individual CD4⁺CD8⁺ (double positive, DP) thymocytes make a decision to differentiate into either CD4⁺ or CD8⁺ T cells. However, the molecular event(s) that defines lineage commitment is controversial. We have previously proposed that lineage commitment in DP thymocytes can be molecularly defined as the selective termination of CD4 or CD8 coreceptor synthesis. The present study supports such a molecular definition by showing that termination of either CD4 or CD8 synthesis is a highly regulated event that is only evident within the most differentiated DP subset (CD5^hiCD69^hiTCR^hibcl-2^hi). In fact, essentially all cells within this DP subset actively synthesize only one coreceptor molecule. In addition, the present results identify three distinct subpopulations of DP thymocytes that define the developmental progression of the lineage commitment process and demonstrate that lineage commitment is coincident with upregulation of TCR and bcl-2. Thus, this study supports a molecular definition of lineage commitment and uniquely identifies TCR^hibcl-2^hi DP thymocytes as cells that are already committed to either the CD4 or CD8 T cell lineage.

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

This article has been cited by other articles:

• Adoro, S., Erman, B., Sarafova, S. D., Van Laethem, F., Park, J.-H., Feigenbaum, L., Singer, A. (2008). Targeting CD4 Coreceptor Expression to Postselection Thymocytes Reveals That CD4/CD8 Lineage Choice Is neither Error-Prone nor Stochastic. J. Immunol. 181: 6975-6983 [Abstract] [Full Text]  
• Oda, H., Suzuki, H., Sakai, K., Kitahara, S., Patrick, M. S., Azuma, Y., Sugi, K., Kitamura, T., Kaye, J., Shirai, M. (2007). Rac1-mediated Bcl-2 induction is critical in antigen-induced CD4 single-positive differentiation of a CD4+CD8+ immature thymocyte line. J. Leukoc. Biol. 81: 500-508 [Abstract] [Full Text]  
• Swat, W., Montgrain, V., Doggett, T. A., Douangpanya, J., Puri, K., Vermi, W., Diacovo, T. G. (2006). Essential role of PI3K{delta} and PI3K{gamma} in thymocyte survival. Blood 107: 2415-2422 [Abstract] [Full Text]  
• Nishida, T., Matsuki, Y., Ono, T., Oguma, T., Tsujimoto, K., Sato, M., Tadakuma, T. (2004). The Novel Murine CD4+CD8+ Thymocyte Cell Line Exhibits Lineage Commitment into Both CD4+ and CD8+ T Cells by Altering the Intensity and the Duration of Anti-CD3 Stimulation In Vitro. J. Immunol. 172: 6634-6641 [Abstract] [Full Text]  
• Mulroy, T., Xu, Y., Sen, J. M. (2003). {beta}-Catenin expression enhances generation of mature thymocytes. Int Immunol 15: 1485-1494 [Abstract] [Full Text]  
• Doan, L. L., Kitay, M. K., Yu, Q., Singer, A., Herblot, S., Hoang, T., Bear, S. E., Morse, H. C. III, Tsichlis, P. N., Grimes, H. L. (2003). Growth Factor Independence-1B Expression Leads to Defects in T Cell Activation, IL-7 Receptor {alpha} Expression, and T Cell Lineage Commitment. J. Immunol. 170: 2356-2366 [Abstract] [Full Text]  
• Liu, X., Adams, A., Wildt, K. F., Aronow, B., Feigenbaum, L., Bosselut, R. (2003). Restricting Zap70 Expression to CD4+CD8+ Thymocytes Reveals a T Cell Receptor-dependent Proofreading Mechanism Controlling the Completion of Positive Selection. JEM 197: 363-373 [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]  
• Mariathasan, S., Zakarian, A., Bouchard, D., Michie, A. M., Zuniga-Pflucker, J. C., Ohashi, P. S. (2001). Duration and Strength of Extracellular Signal-Regulated Kinase Signals Are Altered During Positive Versus Negative Thymocyte Selection. J. Immunol. 167: 4966-4973 [Abstract] [Full Text]  
• Nawijn, M. C., Ferreira, R., Dingjan, G. M., Kahre, O., Drabek, D., Karis, A., Grosveld, F., Hendriks, R. W. (2001). Enforced Expression of GATA-3 During T Cell Development Inhibits Maturation of CD8 Single-Positive Cells and Induces Thymic Lymphoma in Transgenic Mice. J. Immunol. 167: 715-723 [Abstract] [Full Text]  
• Jimenez, E., Vicente, A., Sacedon, R., Munoz, J. J., Weinmaster, G., Zapata, A. G., Varas, A. (2001). Distinct Mechanisms Contribute to Generate and Change the CD4:CD8 Cell Ratio During Thymus Development: A Role for the Notch Ligand, Jagged1. J. Immunol. 166: 5898-5908 [Abstract] [Full Text]  
• Kremer, L., Carramolino, L., Goya, I., Zaballos, A., Gutierrez, J., del Carmen Moreno-Ortiz, M., Martinez-A., C., Marquez, G. (2001). The Transient Expression of C-C Chemokine Receptor 8 in Thymus Identifies a Thymocyte Subset Committed to Become CD4+ Single-Positive T Cells. J. Immunol. 166: 218-225 [Abstract] [Full Text]  
• Yassai, M., Gorski, J. (2000). Thymocyte Maturation: Selection for In-Frame TCR {alpha}-Chain Rearrangement Is Followed by Selection for Shorter TCR {beta}-Chain Complementarity-Determining Region 3. J. Immunol. 165: 3706-3712 [Abstract] [Full Text]  
• Bhandoola, A., Kithiganahalli, B., Granger, L., Singer, A. (2000). Programming for cytotoxic effector function occurs concomitantly with CD4 extinction during CD8+ T cell differentiation in the thymus. Int Immunol 12: 1035-1040 [Abstract] [Full Text]  
• Zhou, X.-Y., Yashiro-Ohtani, Y., Toyo-oka, K., Park, C.-S., Tai, X.-G., Hamaoka, T., Fujiwara, H. (2000). CD5 Costimulation Up-Regulates the Signaling to Extracellular Signal-Regulated Kinase Activation in CD4+CD8+ Thymocytes and Supports Their Differentiation to the CD4 Lineage. J. Immunol. 164: 1260-1268 [Abstract] [Full Text]  
• Keefe, R., Dave, V., Allman, D., Wiest, D., Kappes, D. J. (1999). Regulation of Lineage Commitment Distinct from Positive Selection. Science 286: 1149-1153 [Abstract] [Full Text]  
• Kirchner, J., Bevan, M. J. (1999). ITM2A Is Induced during Thymocyte Selection and T Cell Activation and Causes Downregulation of CD8 when Overexpressed in CD4+CD8+ Double Positive Thymocytes. JEM 190: 217-228 [Abstract] [Full Text]  
• Azzam, H. S., Grinberg, A., Lui, K., Shen, H., Shores, E. W., Love, P. E. (1998). CD5 Expression Is Developmentally Regulated By T Cell Receptor (TCR) Signals and TCR Avidity. JEM 188: 2301-2311 [Abstract] [Full Text]  
• Chan, S., Correia-Neves, M., Dierich, A., Benoist, C., Mathis, D. (1998). Visualization of CD4/CD8 T Cell Commitment. JEM 188: 2321-2333 [Abstract] [Full Text]  
• Williams, O., Norton, T., Halligey, M., Kioussis, D., Brady, H. J.M. (1998). The Action of Bax and Bcl-2 on T Cell Selection. JEM 188: 1125-1133 [Abstract] [Full Text]  
• Suzuki, H., Shinkai, Y., Granger, L. G., Alt, F. W., Love, P. E., Singer, A. (1997). Commitment of Immature CD4+8+ Thymocytes to the CD4 Lineage Requires CD3 Signaling but Does Not Require Expression of Clonotypic T Cell Receptor (TCR) Chains. JEM 186: 17-23 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS