Augmentation of Human Cytotoxic T Lymphocytes against Autologous Tumor by a Factor Released from Human Monocytic Leukemia Cell Line

Abstract

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.