DEVELOPMENT OF CD4 AND CD8 SINGLE POSITIVE T-CELLS IN HUMAN THYMUS ORGAN-CULTURE - IL-7 PROMOTES HUMAN T-CELL PRODUCTION BY SUPPORTING IMMATURE T-CELLS

This paper describes novel model systems to study the development of h uman T cells, Fragments of neonatal human thymus (HUNT) can be culture d in vitro; the initial majority population of CD4, CD8 double-positiv e (DP) thymocytes is not maintained in organ culture. These cells are rapidly replaced by populations of CD4 or CD8 single-positive (SP) T c ells. In addition, allogeneic thymic chimeras can be established by th e addition of human cord blood (HUCB) mononuclear cells as a source of T progenitor FC cells to the organ cultures. Culture results in gd th e acquisition of a mature SP T cell phenotype by the donor cells simil ar to that found when HUCB is allowed to develop in xenogeneic murine scid/scid fetal thymus organ culture. The number of immature and matur e T cells produced by organ cultures can be differentially increased b y the addition of exogenous IL-7, stem cell growth factor, IL-1, or GM -CSF. Anti-IL-7 antibody inhibits T cell production. Taken together, t he results suggest that human T cell development occurs in these in vi tro systems in a similar manner, regardless of the species origin of t he thymic stromal cells in the culture, and that exogenous cytokines c an be used to expand subpopulations of developing T cells. Copyright ( C) 1996 Elsevier Science Ltd.