Alpha Beta/Gamma Delta T Cell Lineage Outcome Is Regulated By Intrathymic Cell Localization And Environmental Signals

alpha beta and gamma delta T cells are two distinct sublineages that develop in the vertebrate thymus. Thus far, their differentiation from a common progenitor is mostly understood to be regulated by intrinsic mechanisms. However, the proportion of alpha beta/gamma delta T cells varies in different vertebrate taxa. How this process is regulated in species that tend to produce a high frequency of gamma delta T cells is unstudied. Using an in vivo teleost model, the medaka, we report that progenitors first enter a thymic niche where their development into gamma delta T cells is favored. Translocation from this niche, mediated by chemokine receptor Ccr9b, is a prerequisite for their differentiation into alpha beta T cells. On the other hand, the thymic niche also generates opposing gradients of the cytokine interleukin-7 and chemokine Ccl25a, and, together, they influence the lineage outcome. We propose a previously unknown mechanism that determines the proportion of alpha beta/gamma delta lineages within species.