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Engel I , Hammond K , Sullivan BA , He X , Taniuchi I , Kappes D , Kronenberg M
Co-receptor choice by V alpha 14i NKT cells is driven by Th-POK expression rather than avoidance of CD8-mediated negative selection
Journal of Experimental Medicine. 2010 May;207(5) :1015-1029
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Mouse natural killer T (NKT) cells with an invariant V alpha 14-J alpha 18 rearrangement (V alpha 14 invariant [V alpha 14i] NKT cells) are either CD4(+)CD8(-) or CD4(-)CD8(-). Because transgenic mice with forced CD8 expression in all T cells exhibited a profound NKT cell deficit, the absence of CD8 has been attributed to negative selection. We now present evidence that CD8 does not serve as a coreceptor for CD1d recognition and that the defect in development in CD8 transgene homozygous mice is the result of a reduction in secondary T cell receptor alpha rearrangements. Thymocytes from mice hemizygous for the CD8 transgene have a less severe rearrangement defect and have functional CD8(+) V alpha 14i NKT cells. Furthermore, we demonstrate that the transcription factor Th, Poxviruses and Zinc finger, and Krupel family (Th-POK) is expressed by V alpha 14i NKT cells throughout their differentiation and is necessary both to silence CD8 expression and for the functional maturity of V alpha 14i NKT cells. We therefore suggest that Th-POK expression is required for the normal development of V alpha 14i NKT cells and that the absence of CD8 expression by these cells is a by-product of such expression, as opposed to the result of negative selection of CD8-expressing V alpha 4i NKT cells.
Engel, Isaac Hammond, Kirsten Sullivan, Barbara A. He, Xi Taniuchi, Ichiro Kappes, Dietmar Kronenberg, Mitchell Rockefeller univ press New york 593kb