Generation of human gamma delta T-cell repertoires

The nature of how the human gamma delta T-cell repertoire is generated duri ng normal development is poorly understood. Unlike TCR-alpha beta(+) cells that are almost exclusively dependent upon the thymus for their development and maturation, gamma delta T cells can be generated in extrathymic sites. The focus of this article is to understand how the human gamma delta T-cel l repertoire is generated during normal human development before and after birth. The expressed repertoire is a reflection of many mechanisms operatin g at both the DNA and protein levels, and we describe the features of the o bserved repertoires in various tissues in fetal and postnatal development a nd in the adult, and the potential mechanisms that account for them. Identi fying the site(s) of origin and understanding how the various subsets of ga mma delta T cells are generated is important for understanding their functi on. In addition, understanding how the gamma delta T-cell repertoire is mod ulated during life by infection, inflammation, and cancer should also bring us closer to understanding its function.