Differential expression of natural killer cell receptors (CD94/NKG2A) on T cells by the stimulation of G-CSF-mobilized peripheral blood mononuclear cells with anti-CD3 monoclonal antibody and cytokines: a study in stem cell donors.
We investigated the expression of the inhibitory NKR (CD94/NKG2A) of the G-CSF mobilized peripheral blood mononuclear cells (G-PBMC) on T cells after stimulation for 7 days by immobilized anti-CD3 monoclonal antibody (mAb) with or without cytokines. We demonstrated increased expression of CD94/NKG2A on CD3+/CD8+ T cells. Also, addition of IL-12 induced significantly more CD94/NKG2A expression than addition of IL-15: CD94+CD3+/NKG2A+CD3+; 43.8 +/- 11.6%/33.7 +/- 11.4% by IL-12 versus 32.8 +/- 13.2%/21.3 +/- 9.6% by IL-15, respectively (n = 9, P < .05). However, >90% purified CD94+ cells CD94+ obtained from IL-15-treated G-PBMC by magnetic cell sorting (MACS) exhibited higher cytolytic (CTL) activity against K562 cells than that from IL-12-treated G-PBMC: E:T = 20:1, 40.7 +/- 18.4% vs 15.1 +/- 5.2% (n = 5, P < .05). Therefore, the cytokine effects on inhibitory NKR expression on T cells and CTL activity are differently regulated. Based on these findings, it may be possible to establish the effective strategy to expand inhibitory NKR-expressing T cells with CTL activity for cell therapy.
Tanaka
J
J
Hematology and Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Toubai
T
T
Miura
Y
Y
Tsutsumi
Y
Y
Kato
N
N
Umehara
S
S
Toyoshima
N
N
Ohta
S
S
Asaka
M
M
Imamura
M
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics*; D019520:Living Donors; D008213:Lymphocyte Activation; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000235:genetics*; D055607:Receptors, Natural Killer Cell; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D016207:Cytokines; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D016179:Granulocyte Colony-Stimulating Factor