Reconstitution of immune systems in RAG2-/- mice by transfer with interleukin-12-induced splenic hematopoietic progenitor cells.
The administration of a high dose of IL-12 into the mice resulted in the induction of splenomegaly. From the flow cytometry analysis of cellularity in an enlarged spleen, it was demonstrated that Thyl.2-CD45RB-c-Kit + Sca-1 + Lin- hematopoietic progenitor cells markedly increased in IL-12-administered mouse spleen compared with untreated mouse spleen. The IL-12-induced hematopoietic progenitor cells showed a greatly enhanced colony-forming activity in CFU-granulocyte/macrophage (CFU-GM), blast-forming units-erythroid (BFU-E) and CFU-spleen (CFU-S) assay. Moreover, it was initially demonstrated that the transfer of IL-12-induced splenic hematopoietic progenitor cells into immunodeficient RAG2-/- mice caused a complete reconstitution of their immune functions including T- and B-cell-mediated immunity. Thus, the evidence that IL-12 has a capability of inducing hematopoietic progenitor cells possessing stem cell-like activity in vivo, indicated another important immunomodulating activity of IL-12 in immunotherapy.
Yahata
T
T
Department of Immunology, Tokai University School of Medicine, Bohseidai, Isehara, Japan.
Ando
K
K
Watanabe
K
K
Mori
T
T
Ohta
A
A
Ohmi
Y
Y
Iwakabe
K
K
Kuge
S
S
Nakui
M
M
Ito
M
M
Habu
S
S
Yasuda
S
S
Nishimura
T
T
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013163:Splenomegaly / Q000139:chemically induced / Q000276:immunology
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D018664:Interleukin-12