Id3 and Id2 act as a dual safety mechanism in regulating the development and population size of innate-like γδ T cells.

Journal Article (Journal Article)

The innate-like T cells expressing Vγ1.1 and Vδ6.3 represent a unique T cell lineage sharing features with both the γδ T and the invariant NKT cells. The population size of Vγ1.1(+)Vδ6.3(+) 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 Vγ1.1(+)Vδ6.3(+) 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 Vγ1.1(+)Vδ6.3(+) T cell expansion. The Vγ1.1(+)Vδ6.3(+) 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 Vγ1.1(+)Vδ6.3(+) 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 γδ T cells. These regulatory effects of Id2 and Id3 on Vγ1.1(+)Vδ6.3(+) T cells are mediated by titration of E protein activity, because removing one or more copies of E protein genes can restore Vγ1.1(+)Vδ6.3(+) 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 γδ lineage through modulating a proper threshold of E proteins.

Full Text

Duke Authors

Cited Authors

  • Zhang, B; Lin, Y-Y; Dai, M; Zhuang, Y

Published Date

  • February 1, 2014

Published In

Volume / Issue

  • 192 / 3

Start / End Page

  • 1055 - 1063

PubMed ID

  • 24379125

Pubmed Central ID

  • PMC3899720

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1302694


  • eng

Conference Location

  • United States