J. Exp. Med.
Volume 186, Number 1, July 7, 1997 17-23

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

By Harumi Suzuki,^* Yoichi Shinkai, Lawrence G. Granger,^* Frederick W. Alt, Paul E. Love,^§ and Alfred Singer^*

From the ^* Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892; the  Howard Hughes Medical Institute and Department of Genetics and Pediatrics, The Children's Hospital, and the Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115; and the ^§ Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20892

As a consequence of positive selection in the thymus, immature CD4⁺8⁺ double-positive, [DP] thymocytes selectively terminate synthesis of one coreceptor molecule and, as a result, differentiate into either CD4⁺ or CD8⁺ T cells. The decision by individual DP thymocytes to terminate synthesis of one or the other coreceptor molecule is referred to as lineage commitment. Previously, we reported that the intrathymic signals that induced commitment to the CD4 versus CD8 T cell lineages were markedly asymmetric. Notably, CD8 commitment appeared to require lineage-specific signals, whereas CD4 commitment appeared to occur in the absence of lineage-specific signals by default. Consequently, it was unclear whether CD4 commitment, as revealed by selective termination of CD8 coreceptor synthesis, occurred in all DP thymocytes, or whether CD4 commitment occurred only in T cell receptor (TCR)-CD3-signaled DP thymocytes. Here, we report that selective termination of CD8 coreceptor synthesis does not occur in DP thymocytes spontaneously. Rather, CD4 commitment in DP thymocytes requires signals transduced by either CD3 or  chains, which can signal CD4 commitment even in the absence of clonotypic TCR chains.

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