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 human T cells. Fragments of neonatal human thymus (HUNT) can be cultured in vitro; the initial majority population of CD4, CD8 double-positive (DP) thymocytes is not maintained in organ culture. These cells are rapidly replaced by populations of CD4 or CD8 single-positive (SP) T cells. In addition, allogeneic thymic chimeras can be established by the addition of human cord blood (HUCB) mononuclear cells as a source of T progenitor cells to the organ cultures. Culture results in the acquisition of a mature SP T cell phenotype by the donor cells similar to that found when HUCB is allowed to develop in xenogeneic murine scid/scid fetal thymus organ culture. The number of immature and mature T cells produced by organ cultures can be differentially increased by 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, the results suggest that human T cell development occurs in these in vitro systems in a similar manner, regardless of the species origin of the thymic stromal cells in the culture, and that exogenous cytokines can be used to expand subpopulations of developing T cells.
Yeoman
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Department of Microbiology and Immunology, University of Arizona, Tucson 85721, USA.
Clark
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DR
DeLuca
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002675:Child, Preschool; D005312:Fetal Blood / Q000502:physiology; D006801:Humans; D007223:Infant; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000276:immunology
D015851:Interleukin-7