In:
The Journal of Immunology, The American Association of Immunologists, Vol. 190, No. 1_Supplement ( 2013-05-01), p. 60.7-60.7
Abstract:
γδ cells include prototypic “innate-like” T cells that cast new light on lymphocyte biology. For example, many have their functions developmentally pre-programmed in the thymus so that they can respond more rapidly to challenge than can conventional T cells. Likewise, rather than deleting them or converting them to T-regs, agonist engagement in the thymus reportedly skews γδ cells toward IFN-γ-producing effectors. Conversely, those cells that do not engage agonist default to IL-17 production. Paradoxically however, thymic progenitors of CD27(-) IL-17-producing γδ cells are TCRhiCD127hiCD44hi which is typical of pre-activated cells, whereas the phenotype of most CD27(+) IFN-γ producers is typical of naïve T cells. To explore this paradox, we examined the SKG mouse which carries a hypomorphic ZAP70 mutation, thus attenuating TCR signaling but retaining TCR expression so that γδ T cell subsets can be identified. Unexpectedly, reducing TCR-signaling largely prevented the development of IL-17-producing γδ cells, whereas IFN-γ-producing γδ cells appeared normal. Nonetheless, deeper analysis showed that IFN-γ-producing γδ cells with the phenotype of agonist selection were depleted. These data permit a revised model in which there are two pathways of γδ T cell development. One gives rise to innate-like T cells that require a developmental TCR signal; from the other, cells biased toward IFN-γ emerge as adaptive cells, without significant dependence on developmental TCR signaling.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.190.Supp.60.7
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2013
detail.hit.zdb_id:
1475085-5
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