Thymus-independent T-cell differentiation in vitro.
The generation of large quantities of novel human T-cell clones ex vivo would make a wide range of gene- and immuno-therapies for tumours and viral infections possible. Several techniques have been described to generate, in vitro and in vivo (using xenogenic hosts), mature T cells from fetal-neonatal and adult human CD34+ cells. All these techniques are cumbersome and cannot be easily translated into clinical protocols because they involve co-cultivation of CD34+ cells with thymic fragments from either human or murine fetuses. We report that the mononuclear cells of human cord blood contain a cell population that supports the differentiation of CD34+ cells into CD4+ or CD8+ naive T cells in serum-deprived cultures stimulated with stem cell factor and interleukin 7. CD4+ or CD8+ CD45RA+ TCRalphabeta+ T cells were continuously produced in vitro over a period of 20 d under these conditions. The generation of T cells in these cultures was a dynamic process and clones of T cells expressing new T-cell receptor beta-chain rearrangements were generated over time. These results pave the way for the development of very simple culture conditions for ex-vivo production of naive helper or cytotoxic T cells which could be very useful for gene- and immuno-therapy of human diseases.
Sanchez
M
M
Laboratorio di Biologia Cellulare, Istituto Superiore di Sanità, Rome, Italy.
Alfani
E
E
Visconti
G
G
Passarelli
A M
AM
Migliaccio
A R
AR
Migliaccio
G
G
D000328:Adult; D018952:Antigens, CD34; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology
D018952:Antigens, CD34; D015851:Interleukin-7; D019089:Stem Cell Factor