The Journal of Experimental Medicine
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Published online 21 August 2000.
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© The Rockefeller University Press, 0022-1007/2000/8/537/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 4, August 21, 2000 537-548

Original Article

Premature Expression of T Cell Receptor (TCR){alpha}ß Suppresses TCR{gamma}{delta} Gene Rearrangement but Permits Development of {gamma}{delta} Lineage T Cells

Kathleen Terrencea, Christian P. Pavlovicha, Errin O. Matechaka, and B.J. Fowlkesa
a Laboratory of Cellular and Molecular Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0420

Correspondence to: B.J. Fowlkes, Bldg. 4, Rm. 111, Laboratory of Cellular and Molecular Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0420. Tel:301-496-5530 Fax:301-402-4891 E-mail:bfowlkes{at}nih.gov.

The T cell receptor (TCR){gamma}{delta} and the pre-TCR promote survival and maturation of early thymocyte precursors. Whether these receptors also influence {gamma}{delta} versus {alpha}ß lineage determination is less clear. We show here that TCR{gamma}{delta} gene rearrangements are suppressed in TCR{alpha}ß transgenic mice when the TCR{alpha}ß is expressed early in T cell development. This situation offers the opportunity to examine the outcome of {gamma}{delta} versus {alpha}ß T lineage commitment when only the TCR{alpha}ß is expressed. We find that precursor thymocytes expressing TCR{alpha}ß not only mature in the {alpha}ß pathway as expected, but also as CD4-CD8- T cells with properties of {gamma}{delta} lineage cells. In TCR{alpha}ß transgenic mice, in which the transgenic receptor is expressed relatively late, TCR{gamma}{delta} rearrangements occur normally such that TCR{alpha}ß+CD4-CD8- cells co-express TCR{gamma}{delta}. The results support the notion that TCR{alpha}ß can substitute for TCR{gamma}{delta} to permit a {gamma}{delta} lineage choice and maturation in the {gamma}{delta} lineage. The findings could fit a model in which lineage commitment is determined before or independent of TCR gene rearrangement. However, these results could be compatible with a model in which distinct signals bias lineage choice and these signaling differences are not absolute or intrinsic to the specific TCR structure.

Key Words: lineage commitment, TCR transgenic mice, thymus, differentiation, positive selection


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