Induction of differentiation of pre-NKT cells to mature Valpha14 NKT cells by granulocyte/macrophage colony-stimulating factor.
Valpha14 NKT cells express an invariant antigen receptor encoded by Valpha14 and Jalpha281 gene segments as well as natural killer (NK) markers, including NK1.1. Here, we describe a precursor population of NKT cells (pre-NKT) that expresses NK1.1, T cell antigen receptor beta, pTalpha, and RAG1/2 but not Valpha14 and surface CD3epsilon. Such pre-NKT cells were differentiated successfully in vitro into mature CD3epsilon+ Valpha14(+) NKT cells by IL-15 and granulocyte/macrophage colony-stimulating factor (GM-CSF) in conjunction with stroma cells. Interestingly, only GM-CSF without stroma cells induced the Valpha14-Jalpha281 gene rearrangement in the pre-NKT cells. This also was confirmed by the findings that the number of mature Valpha14 NKT cells and the frequency of Valpha14-Jalpha281 rearrangements were decreased significantly in the mice lacking a GM-CSF receptor component, common beta-chain. These results suggest a crucial role of GM-CSF in the development of Valpha14 NKT cells in vivo.
Sato
H
H
Core Research for Evolutional Science and Technology (CREST), Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba University School of Medicine 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 Japan.
Nakayama
T
T
Tanaka
Y
Y
Yamashita
M
M
Shibata
Y
Y
Kondo
E
E
Saito
Y
Y
Taniguchi
M
M
D000818:Animals; D000941:Antigens / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000950:Antigens, Ly; D000954:Antigens, Surface; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000276:immunology*
D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor