In vitro Stimulation of Tumor - Draining Lymph Node Lymphocytes with the 30 kDa Antigen of Mycobacterium tuberculosis Leads to the Differentiation of Th1 Cells and Cytotoxic Effector Cells

Park, Jeong Kyu; Paik, Tae Hyun; Koh, Seok Shin; Kim, Hwa Jung; Jo, Eun Kyeong

Abstract

Tumor-draining lymph node (TDLN) lymphocytes contain immunologically sensitized to tumor but functionally deficient T cells. The 30 kDa protein antigen, a major secreted protein antigen of Mycobacterium tuberculosis, exhibits strong T cell stimulatory effect. In this study, it examined that the feasibility of using M tuberculosis 30 kDa antigen to stimulate tumor-draining lymph node cells for the generation of specific immune effector cells. Freshly isolated TDLN lymphocytes could directly respond to the 30 kDa antigen alone and their proliferative responses were markedly augmented by stimulation with rIL-2. TDLN cells were stimulated with the 30 kDa antigen for various time intervals and examined for the induction of IFN-r and IL-4 mRNA using RT-PCR. The expression of IFN-r mRNA was greatly augmented after 1 wk, whereas IL-4 mRNA is markedly decreased after 1 wk. Cytotoxic T cell activities induced by the 30 kDa antigen was also evaluated. TDLN cells stimulated with the 30 kDa antigen alone were able to generate remarkable cytotoxic response to K562 or Daudi cell lines after 6 days of culture. And their cytotoxic effects were highly augmented by stirnulation with rIL-2. These results suggest that the 30 kDa antigen of M. tuberculosis may selectively activate Thl cells of TDLN lymhocytes and induce the cytotoxic T cell activities. In conclusion, the 30 kDa antigen can be used as a biologic response modifier in tumor immunology.