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

ABSTRACT: The innate-like T cells expressing V?1.1 and V?6.3 represent a unique T cell lineage sharing features with both the ?? T and the invariant NKT cells. The population size of V?1.1(+)V?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?1.1(+)V?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?1.1(+)V?6.3(+) T cell expansion. The V?1.1(+)V?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?1.1(+)V?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 ?? T cells. These regulatory effects of Id2 and Id3 on V?1.1(+)V?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?1.1(+)V?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 ?? lineage through modulating a proper threshold of E proteins.


PROVIDER: S-EPMC3899720 | BioStudies | 2014-01-01

REPOSITORIES: biostudies

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