EARLY EVENTS IN HUMAN T CELL ONTOGENY Phenotypic Characterization and Immunohistologic Localization of T Cell Precursors in Early Human Fetal Tissues BY BARTON

During early fetal ontogeny in birds, the epithelial thymic rudiment is colonized by T cell precursors at specific developmentally regulated time intervals (1, 2) . Avian yolk sac, bone marrow, and to a lesser degree, spleen and bursa of fabricius contain hematopoietic cell precursors that are able to migrate to thymic rudiments and give rise to T lymphocytes (2, 3) . In vitro studies using embryonic mouse thymic cultures have similarly demonstrated that hematopoietic cells in fetal yolk sac, bone marrow, and fetal liver can migrate to and colonize 10-d thymic epithelial rudiments (4, 5) . Using avian thymic rudiment cultures and bone marrow cells, thymic epithelial cell-derived chemotactic peptides have been defined that are secreted during the time that the thymic microenvironment is colonized by T cell precursors (6) . Moreover, the phenomenon of avian thymic rudiment colonization by sequential cohorts of T cell precursors in waves has been shown to be due to developmentally regulated periods of thymic epithelial cell production of chemotactic peptides (2, 3, 6) . While it is known that hematopoietic cell precursors are present in embryonic tissues before periods of thymic rudiment colonization by T cell precursors (1, 7), little is known regarding the identification via cell marker expression ofT cell precursors in avian (8) mouse (5, 9, 10) or human (11, 12) fetal tissues before precursor cell entry into the thymus . In our previous studies ofone human fetal tissue before hematopoietic cell colonization of the epithelial thymic rudiment, we identified CD7+, CD45 + (T200 + ) cells in perithymic mesenchyme, and demonstrated that the CD7 T antigen (13-15) is the only known T lineage marker expressed on fetal hematopoietic cells before lymphoid cell colonization ofthe thymus (16) . Moreover, we demonstrated that in man, the critical window of time for thymic development is between 7 and 14 wk of fetal gestation (16) . This early time of colonization of the human thymus has hampered both the identification of fetal T cell precursors and the study of early differentiation events of human T cells .