B7-1(CD80)-transfected human glioma cells and interleukin-12 directly stimulate allogeneic CD8+ T cells.
To obtain more effective cytotoxic T lymphocytes (CTLs), we examined the effect of B7 costimulation and interleukin-12 (IL-12) on the induction of allogeneic CTLs. Peripheral blood lymphocytes (PBLs) or positively selected human CD8+ T cells (purity > 99%) from healthy donors were used as effector cells, and B7-1-transfected or nontransfected U251 human glioma cells (U251-B7 or U251-Vec.) were used as stimulator cells. In mixed lymphocyte culture (MLC) with PBLs and U251 cells, nonspecific natural killer (NK) activity was raised by addition of IL-12, and the effect of B7 costimulation was not observed. However, in MLC with CD8+ T cells, efficient proliferation, generation of CTLs, and cytokine production were induced by MLC with U251-B7 in the presence of IL-12. Efficient generation of CTLs was not induced by either MLC with U251-B7 alone or the addition of IL-12 alone. Our results indicate that a combination of B7-1 costimulation and IL-12 is effective for inducing generation of CTLs, and that the CD8+ T cells can be differentiated into CTLs without the help of CD4+ T cells or antigen-presenting cells or both.
Komata
T
T
Department of Neurosurgery, College of Biomedical Technology, Niigata University, Japan.
Tanaka
R
R
Yamamoto
K
K
Oda
T
T
Ono
K
K
Yoshida
S
S
Takahashi
M
M
D018122:B7-1 Antigen / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D016207:Cytokines; D018664:Interleukin-12