Interleukin 7-engineered stromal cells: a new approach for hastening naive T cell recruitment.
In this study we determined whether human stromal cells could be engineered with a retroviral vector carrying the interleukin 7 (IL-7) gene and investigated the effects on T cells in vitro and in vivo in a murine model. Transduced mesenchymal cells strongly express CD90 (98.15%), CD105 (87.6%), and STRO-1 (86.7%). IL-7 production was 16.37 (+/-2 SD) pg/ml, which remained stable for 60 days. In vitro-immunoselected naive T cells maintained the CD45RA+ CD45RO- naive phenotype (4.2 times more than controls) after 7 days of culture with IL-7-engineered stromal cells. The apoptosis rate (4.7%) of the naive T cells cultured with transduced stromal cells overlapped with that of freshly isolated cells. Immunohistological analysis detected stromal cells in bone marrow, spleen, and thymus. Cotransplantation of IL-7-engineered stromal cells with CD34+ cells improved engraftment in terms of CD45+ cells and significantly increased the CD3+ cell count in peripheral blood, bone marrow, and spleen. These data demonstrate the following: (1) human stromal cells can be transduced, generating a normal layer; (2) transduced stromal cells in vitro maintain the naive T cell phenotype; and (3) IL-7-transduced stromal cells in vivo home to lymphoid organs and produce sufficient IL-7 in loco, supporting T cell development in a cotransplantation model. Because of their efficient cytokine production and homing, IL-7-engineered stromal cells might be an ideal vehicle to hasten immunological reconstitution in T cell-depleted hosts.
Di Ianni
Mauro
M
University of Perugia, 06123 Perugia, Italy.
Del Papa
Beatrice
B
De Ioanni
Maria
M
Terenzi
Adelmo
A
Sportoletti
Paolo
P
Moretti
Lorenzo
L
Falzetti
Franca
F
Gaozza
Eugenia
E
Zei
Tiziana
T
Spinozzi
Fabrizio
F
Bagnis
Claude
C
Mannoni
Patrice
P
Bonifacio
Elisabetta
E
Falini
Brunangelo
B
Martelli
Massimo F
MF
Tabilio
Antonio
A
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D017690:Cell Transplantation / Q000379:methods; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012190:Retroviridae / Q000235:genetics; D017154:Stromal Cells / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014161:Transduction, Genetic
D018952:Antigens, CD34; D017252:CD3 Complex; D015851:Interleukin-7; D017493:Leukocyte Common Antigens