The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1996/12/2091/ $5.00
The Journal of Experimental Medicine, Volume 184, Number 6, December 1, 1996 2091-2100


Articles

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

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 (CD5hiCD69hiTCRhibcl-2hi). 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 TCRhibcl-2hi DP thymocytes as cells that are already committed to either the CD4 or CD8 T cell lineage.


Address correspondence to Alfred Singer, Experimental Immunology Branch, NCI/NIH, Building 10 Room 4B-17, Bethesda, MD 20892. Dr. Punt's current address is Haverford College, Biology Department, 370 Lancaster Avenue, Haverford, PA 19041.

1 Abbreviations used in this paper: DN, double negative; DP, double positive; SP, single positive.


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