Knobloch C, Dennert G
University of Southern California, Comprehensive Cancer Center, Los Angeles 90033.
J Immunol. 1988 Feb 1;140(3):744-9.
(C57BL/6 x DBA/2)F1 mice transplanted with parental C57BL/6 spleen cells become splenic chimeras, show donor antihost cytotoxic T cell activity, and lose their T cell-mediated, humoral, and natural immunity. Injection of anti-asialo-GM1 (ASGM1) into transplanted mice strongly suppresses splenic cytotoxic activity and causes a significant reduction of spleen cells expressing ASGM1, Thy-1, and Lyt-2. In vitro treatment of spleen cells from transplanted mice with antibody and complement shows that the cytotoxic effector cells are ASGM1+, Thy-1+, Lyt-2+, L3T4-, NK1.1-, and H-2d-, hence of donor origin. The cytotoxic effector cells are specific for H-2d targets and lack NK activity. In an attempt to explore whether in vivo elimination of the cytotoxic effector cells has any influence on splenic chimerism or humoral immunity, F1 mice injected with parental splenocytes were treated with anti-ASGM 1. Results show that this treatment eliminates a substantial proportion of cytotoxic effector cells but has no effect on splenic chimerism or restoration of humoral immunity. It therefore appears that cytotoxic effector cells are not primarily responsible for induction of chimerism or suppression of humoral immunity. In support of this injection of parental spleen cells with the nu/nu mutation induces killer cells in F1 mice but fails to induce splenic chimerism or immunosuppression. In contrast, injection of parental spleen cells with the bg/bg mutation generates both splenic chimerism and suppression of humoral immunity although their ability to generate cytotoxic effector cells in F1 hosts is seriously impaired and comparable to the cytotoxic potential of C57BL/6 nu/nu cells. It is concluded that the ASGM1 + cytotoxic T cells are not primarily responsible for splenic chimerism and suppression of humoral immunity and that the two effects are likely caused by parental cells with a different phenotype and function.
将亲代C57BL/6脾细胞移植到（C57BL/6×DBA/2）F1小鼠中，会使其成为脾嵌合体，表现出供体抗宿主细胞毒性T细胞活性，并丧失其T细胞介导的、体液性和天然免疫。向移植后的小鼠注射抗唾液酸GM1（ASGM1）可强烈抑制脾脏细胞毒性活性，并导致表达ASGM1、Thy-1和Lyt-2的脾细胞显著减少。用抗体和补体对移植后小鼠的脾细胞进行体外处理表明，细胞毒性效应细胞为ASGM1+、Thy-1+、Lyt-2+、L3T4-、NK1.1-和H-2d-，因此来源于供体。细胞毒性效应细胞对H-2d靶标具有特异性，且缺乏NK活性。为了探究体内清除细胞毒性效应细胞是否对脾嵌合或体液免疫有任何影响，给注射了亲代脾细胞的F1小鼠注射抗ASGM 1。结果表明，这种处理消除了相当一部分细胞毒性效应细胞，但对脾嵌合或体液免疫的恢复没有影响。因此，细胞毒性效应细胞似乎不是诱导嵌合或抑制体液免疫的主要原因。支持这一观点的是，向F1小鼠注射具有nu/nu突变的亲代脾细胞可诱导杀伤细胞，但未能诱导脾嵌合或免疫抑制。相反，注射具有bg/bg突变的亲代脾细胞可产生脾嵌合和体液免疫抑制，尽管它们在F1宿主中产生细胞毒性效应细胞的能力严重受损，且与C57BL/6 nu/nu细胞的细胞毒性潜力相当。结论是，ASGM1+细胞毒性T细胞不是脾嵌合和体液免疫抑制的主要原因，这两种效应可能是由具有不同表型和功能的亲代细胞引起的。
