Augmentation of human cytotoxic T lymphocytes against autologous tumor by a factor released from human monocytic leukemia cell line.
A human acute monocytic leukemia cell line, THP-1, releases a factor which activates human cytotoxic (killer) T lymphocytes (CTL) against autologous tumor in vitro. The factor, named cytotoxic (killer) T cell activating factor (KAF), is an acidic protein of 70,000 to 100,000 dalton molecular size. Peripheral blood leukocytes from two patients, bearing epithelioid sarcoma or malignant schwannoma, were cultured for 7 days with individual autologous tumor to induce CTL directed to the corresponding tumor. Monocyte-depleted peripheral leukocytes generated lesser CTL activity than the monocyte-containing leukocyte population. However, the KAF was able to replace the monocyte function. The KAF acted at the CTL generation phase as well as the effector phase. The KAF-activated killer cells possessed CD4-8+ surface phenotype. The CTL killed autologous tumor or other unrelated tumor cell lines only when they shared some of the HLA class I antigens. It was also demonstrated that the KAF does not activate killer cells without proper antigenic stimuli, because the KAF-augmented CTL possess specificity against autologous tumor or other HLA-A or -B matched tumor cell lines. The therapeutic applicability of human KAF for anti-tumor CTL therapy against autologous tumor is discussed.
Maeda
N
N
Department of Immunology, Kochi Medical School.
Hamasato
S
S
Miyazawa
H
H
Takata
M
M
Yamamoto
H
H
Fujimoto
S
S
D000328:Adult; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology; D016827:CD8 Antigens; D002850:Chromatography, Gel; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D009369:Neoplasms / Q000276:immunology*; D009442:Neurilemmoma / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D012509:Sarcoma / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D016827:CD8 Antigens; D006680:HLA Antigens; D009363:Neoplasm Proteins