@article{oai:twinkle.repo.nii.ac.jp:00016877, author = {SUZUKI, Yoshiyuki and YAMAUCHI, Katsumi and OBATA, Hiroshi and HAYASHI, Naoaki}, issue = {12}, journal = {東京女子医科大学雑誌}, month = {Dec}, note = {HBs抗原に対する免疫学的寛容状態の解明のために我々はHBs抗原特異的抑制性T細胞の誘導のメカニズムについて検討を行った.抑制活性をみるための方法としては,我々がこれまでに報告してきたin vitroにおけるHBs抗体産生系を用いた.まず,HBワクチンで免疫されたhigh responder(HBワクチンに対する高応答者)より得られた末梢血単核球をhigh doseのHBs抗原で刺激し,CD8陽性の抑制性T細胞を誘導した.この抑制性T細胞はHBs抗原に特異的であり,HBs抗体の産生のみを抑制していた.さらにこのCD8陽性抑制性T細胞の誘導にはCD4陽性細胞が必要であり,in vitroにおいてCD4陽性細胞を除くことにより抑制性T細胞の誘導は阻害された.この抑制性T細胞を誘導するCD4陽性細胞(suppressor-inducer T cell)はHLA class 2抗原のDQ抗原に拘束されており,抑制性T細胞を誘導する培養液中に,anti-DQを加えることにより抑制性活性の低下が認められた.この活性の低下は,anti-DQにのみ引き起されるものでありanti-DRや,myeloma proteinでは抑制活性の低下は得られなかった.また,このanti-DQにより阻害されるのはCD4 suppreessor-inducer T cellを介したCD8 suppressor T cell誘導の系であり,抗体産生系の培養中にanti-DQを加えても同様の抑制活性の低下は得られなかった., For a more precise analysis of the immunological tolerance to hepatitis B virus surface antigen (HBsAg), we studied the induction mechanisms of HBsAg-specific suppressor T cells (Ts). The stimulation of peripheral blood mononuclear cells (PBMC) obtained from HB vaccinees with a high dose of HBsAg resulted in the generation of HBsAg-specific Ts. While these activated Ts were CD8 cells, their induction was abrogated by the deletion of CD4 cells prior to the in vitro culture, indicating that CD4 T cells were needed to induce CD8 Ts. An in vitro inhibition study of Ts induction with monoclonal antibodies to major histocompatibility complex class 2 antigens revealed that the induction of Ts was inhibited by and-DQ but not by and-DR. However, anti-DQ inhibition dose not directly affect the suppressive effect of Ts, indicating that HLA-DQ antigen might be required only for the induction of Ts. From these results, we can assume that immune suppression is initiated by the stimulation of CD4 cells by a molecular complex composed of a fragment of HBsAg and HLA-DQ antigen that is expressed on the surface of antigen presenting cells.}, pages = {983--989}, title = {HLA-DQ-RECOGNIZING CD4 CELL REQUIREMENT FOR GENERATING HEPATITIS B SURFACE ANTIGEN-SPECIFIC SUPPRESSOR T CELLS}, volume = {67}, year = {1997} }