GENERATION OF A NOVEL CD8-LYMPHOCYTE THAT REQUIRES SOLUBLE FACTOR TO LYSE AUTOLOGOUS ANTIGEN-PRESENTING CELLS( CYTOTOXIC T)

We reported the existence of high and low responders to the streptococ cal cell wall antigen (SCW) in the human population. To analyze the me chanism of the low responsiveness to SCW at the cellular level, we est ablished SCW-specific CD4+ T cell lines. During the course of generati on of a SCW-specific CD4+ T cell line restricted by HLA-DQ from a low responder, we obtained autoreactive CD8+ cytotoxic T lymphocytes as a cell line (HYCD8). They proliferated in the presence of autologous mon ocytes and IL-2, without SCW HYCD8 lysed autologous monocytes and Epst ein-Barr virus-transformed B lymphoblastoid cell line (BLCL). This cyt otoxic activity was specifically inhibited by an anti-HLA class I fram ework monoclonal antibody and restricted by HLA-B52 or B54 specificity , as judged by killing activity against panel cells and HLA class I-tr ansfected BLCL. It was unique to HYCD8 that the HLA class I-restricted cytotoxicity was observed only in the presence of soluble factor with low molecular mass (< 10(4) Da) produced mainly by B cells, which cou ld not be replaced by known cytokines and their mixtures. We thus desc ribe novel HLA class I-restricted cytotoxic CD8+ T cells that kill ant igen-presenting cells in a soluble factor-dependent manner.