Generation of human gammadelta T-cell repertoires.

The nature of how the human gammadelta T-cell repertoire is generated during normal development is poorly understood. Unlike TCR -alphabeta+ cells that are almost exclusively dependent upon the thymus for their development and maturation, gammadelta T cells can be generated in extrathymic sites. The focus of this article is to understand how the human gammadelta T-cell repertoire is generated during normal human development before and after birth. The expressed repertoire is a reflection of many mechanisms operating at both the DNA and protein levels, and we describe the features of the observed repertoires in various tissues in fetal and postnatal development and in the adult, and the potential mechanisms that account for them. Identifying the site(s) of origin and understanding how the various subsets of gammadelta T cells are generated is important for understanding their function. In addition, understanding how the gammadelta T-cell repertoire is modulated during life by infection, inflammation, and cancer should also bring us closer to understanding its function.