Ghayur T, Seemayer T A, Lapp W S
Department of Physiology, McGill University, Montreal, Quebec, Canada.
Transplantation. 1988 Mar;45(3):586-90. doi: 10.1097/00007890-198803000-00017.
In this study anti-asialo GM1 antibodies (anti-ASGM1) were used to further characterize the effector cells responsible for graft-versus-host (GVH)-induced histopathological lesions: Two different types of ASGM1+ cells were identified: an endogenous ASGM1+ population and an induced ASGM1+ population. Both of the ASGM1+ cell populations exhibited natural killer (NK) cell activity, as assessed by their ability to lyse YAC tumor targets in vitro. Donor C57BL/6 (B6) mice were treated in vivo with anti-ASGM1 to eliminate endogenous ASGM1+ cells. ASGM1+ cells were induced in B6 donor mice by treating the animals with 15 x 10(6) B6 x AF1 (B6AF1) lymphoid cells for 44-48 hr. The induced ASGM1+ cells were eliminated by in vivo treatment with anti-ASGM1. GVH reactions were induced by injecting B6 lymphoid cells into B6AF1 mice. Prior to GVH induction the B6 donor cells were tested for NK cell activity against YAC tumor target cells in vitro and for T and B cell functions by mitogen responses in vitro. GVH reactions were determined by splenomegaly, suppression of the plaque-forming cell (PFC) response to sheep red blood cells (SRBC), suppression of the T and B cell mitogen responses, and the development of GVH-associated histopathological alterations in the thymus, liver, and pancreas. Donor lymphoid cells depleted of endogenous ASGM1+ cells were effective at inducing splenomegaly, severe suppression of immune functions, and histopathological lesions. Donor lymphoid cells depleted of both the endogenous and induced ASGM1+ cells displayed normal T cell mitogen responses and were capable of inducing splenomegaly and partial suppression of the PFC response to SRBC when injected into B6AF1 recipients, however, these lymphoid cells failed to induce both GVH-associated histopathological lesions and severe suppression of T and B cell mitogen responses. These results suggest that semiallogeneic stimulation induces an ASGM1+ population in the donor inoculum that displays NK cell-like function (YAC killing) and that plays a crucial role in inducing GVH-mediated histopathological lesions and severe immunosuppression of both T and B cell responses.
在本研究中，抗去唾液酸GM1抗体（抗-ASGM1）被用于进一步鉴定介导移植物抗宿主（GVH）诱导的组织病理学损伤的效应细胞：鉴定出两种不同类型的ASGM1+细胞：内源性ASGM1+群体和诱导性ASGM1+群体。通过体外裂解YAC肿瘤靶标的能力评估，这两种ASGM1+细胞群体均表现出自然杀伤（NK）细胞活性。给供体C57BL/6（B6）小鼠体内注射抗-ASGM1以清除内源性ASGM1+细胞。通过用15×10(6) B6×AF1（B6AF1）淋巴细胞处理动物44-48小时，在B6供体小鼠中诱导出ASGM1+细胞。通过体内注射抗-ASGM1清除诱导性ASGM1+细胞。通过将B6淋巴细胞注入B6AF1小鼠诱导GVH反应。在诱导GVH之前，体外检测B6供体细胞对YAC肿瘤靶细胞的NK细胞活性以及通过体外有丝分裂原反应检测T和B细胞功能。通过脾肿大、对绵羊红细胞（SRBC）的空斑形成细胞（PFC）反应受抑制、T和B细胞有丝分裂原反应受抑制以及胸腺、肝脏和胰腺中GVH相关组织病理学改变的发生来确定GVH反应。去除内源性ASGM1+细胞的供体淋巴细胞可有效诱导脾肿大、严重抑制免疫功能以及组织病理学损伤。去除内源性和诱导性ASGM1+细胞的供体淋巴细胞表现出正常的T细胞有丝分裂原反应，并且当注入B6AF1受体时能够诱导脾肿大和对SRBC的PFC反应部分受抑制，然而，这些淋巴细胞未能诱导GVH相关组织病理学损伤以及严重抑制T和B细胞有丝分裂原反应。这些结果表明，半同种异体刺激在供体接种物中诱导出具有NK细胞样功能（YAC杀伤）的ASGM1+群体，并且该群体在诱导GVH介导的组织病理学损伤以及严重免疫抑制T和B细胞反应中起关键作用。
