Background and Objective: Polymorphonuclear neutrophils (PMNs) are considered as components that play several important immunoregulatory roles. The aim of this study is to identify soluble mediators in normal human serum that may cause immunological reactions in which PMNs are strongly involved. Methods: For this purpose, the correlation between the amount of several soluble mediators in normal human serum and the cytotoxic activity of the serum against PMNs was investigated. Results: The investigation revealed a strong correlation between the amount of anti-human leukocyte histocompatibility antigen (HLA) class I immunoglobulin isotype M (IgM) antibody (Ab) and serum cytotoxic activity against PMNs, and a reverse correlation between the amount of soluble HLA class I (sHLA-I) in the serum and serum cytotoxic activity against PMNs. We also found that the addition of affinitypurified sHLA-I to anti-human HLA class I IgM-positive serum significantly reduces the serum cytotoxic activity against PMNs. In this case, an immune complex (IC) formed by antihuman HLA class I IgM Ab and purified soluble HLA class I (psHLA-1) markedly decreased serum cytotoxic activity. Moreover, it was observed that the IC formed by anti-HLA-I IgM and sHLA-I bound to PMNs via not only HLA class I antigens but also two kinds of low-affinity receptors for IgG, namely, CD16 and CD32, have protective roles against cytotoxic IgG attack. Conclusion: The present results indicate that anti-HLA class I IgM, sHLA-I and FcyRs are strongly involved in the immunomodulatory reactions of PMNs.

主要組織適合性遺伝子複合体(Major Histocompatibility Gene Complex, MHC)は名称の通り臓器移植時の適合性を担う同種(アロ)抗原の最強のものとして発見され, その後の解析から自己生体内において(外来)非自己抗原をT細胞に提示する役割を担う獲得免疫反応誘導の中心分子であることが判明した. クラスI抗原は全身の殆どの細胞表面に発現し, ペプチド結合溝内に自己ペプチドを結合している場合には正常自己細胞マーカーとして働く一方, ウィルス感染細胞やがん細胞においては細胞内で合成される非自己抗原ペプチドを結合してCD8陽性キラーT細胞に認識させ発現細胞の破壊除去を誘導することで免疫学的監視機構を構築している. 多種多様な異物抗原ペプチドを結合溝内に結合してT細胞受容体に提示するためにクラスI抗原遺伝子座は高度な多型性を獲得したと考えられるが, それは同時に代償として強力なアロ反応性をもつことにもなった. このために移植時においてアロ特異性T細胞やアロ抗体によるクラスI認識反応から強力な拒絶応答やGVHD反応が引き起こされる.