Cytotoxic gammadelta or alphabeta T cells with a natural killer cell marker, CD56, induced from human peripheral blood lymphocytes by a combination of IL-12 and IL-2.
Populations of cytotoxic CD3+CD56+ cells were selectively expanded when monocyte-depleted human PBL (M(-) PBL) were cultured with 20 U/ml IL-12 and 100 U/ml IL-2. In a majority of cases, CD4-CD8- as well as CD8+ gammadelta T cells with CD56 Ag were induced, but in some cases CD4+CD56+ alphabeta T cells were selectively increased. Determination of which will increase, gammadelta or alphabeta T cells, apparently is dependent upon individuals. When M(-) PBL were stimulated with IL-12 and IL-2 in the presence of immobilized anti-CD3 Ab, CD8+CD56+ alphabeta T cells increased exclusively. When M(-) PBL were cultured by IL-2 alone, CD3+CD56- cell expansion was predominant while CD3+CD56+ cells remained a minor population. Cytotoxic activity of M(-) PBL cultured with a combination of IL-12 and IL-2 is much greater than when cultured with IL-2 alone. The cytotoxicity of activated M(-) PBL was abrogated by the depletion of either CD3+ or CD56+ cells irrespective of their gammadelta or alphabeta phenotypes. These types of cells are preferentially present in the livers of humans. The results revealed that, under certain conditions, IL-12 synergizes with IL-2 to induce potent cytotoxic T cells with CD56 Ag of humans, and suggest that these cells in the human liver are functionally similar to NK1+ alphabeta T cells in murine liver.
First Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
M
M
Satoh
S
S
Seki
W
W
Hashimoto
K
K
Ogasawara
T
T
Kobayashi
K
K
Kumagai
S
S
Matsuno
K
K
Takeda
D015415:Biomarkers; D017252:CD3 Complex / Q000032:analysis*; D019002:CD56 Antigen / Q000032:analysis*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000737:chemistry*; D008099:Liver / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*
D015415:Biomarkers; D017252:CD3 Complex; D019002:CD56 Antigen; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12