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CD16 Cross-Linking Blocks Rearrangement of the TCRß Locus and Development of ß T Cells and Induces Development of NK Cells from Thymic Progenitors

Scott K. Durum^1,*, Chong-Kil Lee^*, Theresa M. Geiman, William J. Murphy and Kathrin Muegge

^* Laboratory of Immunoregulation, Division of Basic Sciences, National Cancer Institute, and Science Applications International Corporation, National Cancer Institute, Frederick, MD 21702

Mouse thymocytes normally develop into T lymphocytes, but the embryonic thymus also contains precursor cells capable of developing into NK cells. Here, we describe conditions that induce pro-T cells to develop into NK cells. CD16 is expressed on thymic pro-T cells. We observed that CD16 cross-linking during culture of embryonic thymic organs suppressed rearrangement of the TCRß locus (but did not inhibit TCR locus rearrangement). Rearrangement of the TCRß locus is normally required for development to the CD4⁺CD8⁺, and this development was also suppressed by CD16 cross-linking. The ability of CD16 cross-linking to block ßT cell development was not attributable to toxic effects, but rather was accompanied by promotion of development into NK cells, identified based on molecular and functional criteria. These results suggest that common lymphoid precursors can respond to environmental signals to commit to the ßT vs NK developmental pathways.