CD16 cross-linking blocks rearrangement of the TCR beta locus and development of alpha beta T cells and induces development of NK cells from thymic progenitors.
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 TCR beta locus (but did not inhibit TCR gamma locus rearrangement). Rearrangement of the TCR beta 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 alpha beta T 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 alpha beta T vs NK developmental pathways.
Laboratory of Immunoregulation, Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702-1201, USA. durums@mail.ncifcrf.gov
S K
SK
Durum
C K
CK
Lee
T M
TM
Geiman
W J
WJ
Murphy
K
K
Muegge
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology*; D007106:Immune Sera / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000037:antagonists & inhibitors* / Q000235:genetics*; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D019138:Antibodies, Blocking; D007106:Immune Sera; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017452:Receptors, IgG