科研之友
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摘要
Thymocytes expressing the invariant V gamma 5 gamma delta T-cell receptor represent progenitors of dendritic epidermal T-cells (DETC) that play an important immune surveillance role in the skin. In contrast to the bulk of alpha beta T-cell development, V gamma 5(+) DETC progenitor development occurs exclusively in fetal thymus. Whilst alpha beta T-cell development is known to require chemokine receptor mediated migration through distinct thymus regions, culminating in medullary entry and thymic egress, the importance and control of intrathymic migration for DETC progenitors is unclear. We recently revealed a link between V gamma 5(+) DETC progenitor development and medullary thymic epithelial cells expressing Aire, a known regulator of thymic chemokine expression, demonstrating that normal V gamma 5(+) DETC progenitor development requires regulated intramedullary positioning. Here we investigate the role of chemokines and their receptors during intrathymic V gamma 5(+) DETC progenitor development and establishment of the DETC pool in the skin. We report that thymic medullary accumulation of V gamma 5(+) DETC progenitors is a G-protein coupled receptor dependent process. However, this process occurs independently of Aire%26apos;s influences on intrathymic chemokines, and in the absence of CCR4 and CCR7 expression by DETC progenitors. In contrast, analysis of epidermal gamma delta T-cells at neonatal and adult stages in CCR4(-/-) mice reveals that reduced numbers of DETC in adult epidermis are not a consequence of diminished intrathymic embryonic development, nor deficiencies in initial epidermal seeding in the neonate. Collectively, our data reveal differences in the chemokine receptor requirements for intrathymic migration of alpha beta and invariant gamma delta T-cells, and highlight a differential role for CCR4 in the maintenance, but not initial seeding, of DETC in the epidermis.
- 出版日期2013-9-12
