Evidence for a step - wise program of T cell development within the human tonsil

Human T cell development within the thymus is a well-characterized event, and it is known that a functional thymus is required for normal T cell generation to take place. Individuals with poor thymic function, from either congenital abnormality or post-natal injury, have a difficult time mounting a proper immune response and suffer from debilitating immune deficiency. Thus, it would be highly beneficial to identify an extrathymic human tissue that can support T cell differentiation so that we may eventually augment T cell production in these individuals. However, to date, no definitive site of extrathymic T cell development has been established. In this study, we used flow cytometry to identify five populations of putative extrathymic T cell precursors within the human pediatric tonsil. These populations range from an early CD34CD38Lin subset all the way to a CD1aCD4CD8CD3 double positive pre-T cell. Each subset identified phenotypically resembles the same population found in the human thymus, suggesting that there is considerable similarity between the cells in each of these two tissues. Furthermore, each putative extrathymic T cell developmental intermediate found within the tonsil retains the ability to develop into a mature CD3 T cell. Thus, our data suggest that the human tonsil contains a full spectrum of T cell developmental intermediates that are remarkably similar to those found in the human thymus, and that the tonsil may be an extrathymic site which supports complete T cell differentiation.