[Analysis of autoreactive CD8+ T cells against antigen presenting cells]

We reported the existence of high and low responders to streptococcal cell wall antigen (SCW) in human population. To analyze the mechanism of low responsiveness to SCW at the cellular level, we previously established SCW specific CD4+ T cell lines. During the course of generation of a SCW specific CD4+ T cell line restricted by HLA-DQ from a low responder, we obtained autoreactive CD8+ CTLs. Once the CTL was established as a line (HYCD8), they proliferated in the presence of autologous monocytes and IL-2 without SCW. HYCD8 lysed autologous monocytes and EBV transformed B lymphoblastoid cell line (BLCL). This cytotoxic activity was specifically inhibited by an anti-HLA class I framework mAb and restricted by HLA-B specificity, as judged by killing activity against panel cells and HLA class I-transfected BLCLs. Although HYCD8 contained perforin in the cytoplasm, this HLA-class I restricted cytotoxicity was observed only in the presence of the supernatant of cultured PBLs which could not be replaced by known cytokines and their mixtures. The biological activity of the soluble factor for cytotoxic activity (SFCA) was purified in a single peak fraction by HPLC. Thus, HYCD8 down-regulated the proliferation of SCW specific CD4+ T cells through killing autologous APCs in SFCA dependent manner suggesting a unique immunoregulatory role of autoreactive CD8+ CTLs in immune responses.