Id3 and Id2 Act as a Dual Safety Mechanism in Regulating the Development and Population Size of Innate-like gamma delta T Cells

作者：Zhang Baojun; Lin Yen Yu; Dai Meifang; Zhuang Yuan^*

来源：The Journal of Immunology, 2014, 192(3): 1055-1063.

DOI：10.4049/jimmunol.1302694

The innate-like T cells expressing V gamma 1.1 and V delta 6.3 represent a unique T cell lineage sharing features with both the gamma delta T and the invariant NKT cells. The population size of V gamma 1.1(+)V delta 6.3(+) T cells is tightly controlled and usually contributes to a very small proportion of thymic output, but the underlying mechanism remains enigmatic. Deletion of Id3, an inhibitor of E protein transcription factors, can induce an expansion of the V gamma 1.1(+)V delta 6.3(+) T cell population. This phenotype is much stronger on the C57BL/6 background than on the 129/sv background. Using quantitative trait linkage analysis, we identified Id2, a homolog of Id3, to be the major modifier of Id3 in limiting V gamma 1.1(+)V delta 6.3(+) T cell expansion. The V gamma 1.1(+)V delta 6.3(+) phenotype is attributed to an intrinsic weakness of Id2 transcription from Id2 C57BL/6 allele, leading to an overall reduced dosage of Id proteins. However, complete removal of both Id2 and Id3 genes in developing T cells suppressed the expansion of V gamma 1.1(+)V delta 6.3(+) T cells because of decreased proliferation and increased cell death. We showed that conditional knockout of Id2 alone is sufficient to promote a moderate expansion of gamma delta T cells. These regulatory effects of Id2 and Id3 on V gamma 1.1(+)V delta 6.3(+) T cells are mediated by titration of E protein activity, because removing one or more copies of E protein genes can restore V gamma 1.1(+)V delta 6.3(+) T cell expansion in Id2 and Id3 double conditional knockout mice. Our data indicated that Id2 and Id3 collaboratively control survival and expansion of the gd lineage through modulating a proper threshold of E proteins.

• 出版日期2014-2-1