Journal
INTERNATIONAL IMMUNOLOGY
Volume 27, Issue 4, Pages 205-215Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxu104
Keywords
innate-like T cells; NKT development; thymocyte development
Categories
Funding
- JSPS KAKENHI Grant [23310036, 21790462, 24790465, 26460570]
- Health Labour Sciences Research Grant [201313001A]
- Grant for Promotion of Niigata University Research Projects
- Tsukada Medical Foundation
- Grants-in-Aid for Scientific Research [23310036, 221S0003, 24790465, 21790462] Funding Source: KAKEN
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If Bcl11b activity is compromised, CD4(+)CD8(+) double-positive ( DP) thymocytes produce a greatly increased fraction of innate CD8(+) single-positive ( SP) cells highly producing IFN-gamma, which are also increased in mice deficient of genes such as Itk, Id3 and NF-kappa B1 that affect TCR signaling. Of interest, the increase in the former two is due to the bystander effect of IL-4 that is secreted by promyelocytic leukemia zinc finger-expressing NKT and gamma delta T cells whereas the increase in the latter is cell intrinsic. Bcl11b zinc-finger proteins play key roles in T cell development and T cell-mediated immune response likely through TCR signaling. We examined thymocytes at and after the DP stage in Bcl11b(F/S826G) CD4cre, Bcl11b(F/+) CD4cre and Bcl11b(+/S826G) mice, carrying the allele that substituted serine for glycine at the position of 826. Here we show that Bcl11b impairment leads to an increase in the population of TCR alpha beta(high)CD44(high)CD122(high) innate CD8SP thymocytes, together with two different developmental abnormalities: impaired positive and negative selection accompanying a reduction in the number of CD8SP cells, and developmental arrest of NKT cells at multiple steps. The innate CD8SP thymocytes express Eomes and secrete IFN-gamma after stimulation with PMA and ionomycin, and in this case their increase is not due to a bystander effect of IL-4 but cell intrinsic. Those results indicate that Bcl11b regulates development of different thymocyte subsets at multiple stages and prevents an excess of innate CD8SP thymocytes.
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