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跨次要组织相容性屏障移植的小鼠中与移植物抗宿主反应相关的免疫功能障碍。II. 依赖T细胞的抗体反应中的可逆缺陷。

Immune dysfunction associated with graft-vs-host reaction in mice transplanted across minor histocompatibility barriers. II. Reversible defect in T-dependent antibody responses.

作者信息

Budhecha S, Hamilton B L

机构信息

Department of Biological Structure, University of Washington, Seattle 98195.

出版信息

J Immunol. 1989 Jun 1;142(11):3740-5.

PMID:2523932
Abstract

B cell and Th cell functions were assessed in mice undergoing a graft-vs-host reaction (GvHR) in response to minor histocompatibility Ag by using the plaque-forming cell (PFC) response to the T-independent Ag TNP-Brucella abortus and the T-dependent Ag TNP-SRBC. Bone marrow plus spleen cells from B10.D2 mice were transplanted into lethally irradiated B10.D2 (syngeneic recipient) or H-2d-compatible BALB/c (allogeneic recipient) to produce a chronic form of GvHR. BALB/c recipients of an allogeneic transplant demonstrated a marked and proportional lymphoid depletion of the spleen with normal percentages of B cells, T cells, and CD4+ and CD8+ T cell subsets. Mice with GvHR made normal numbers of PFC/10(5) spleen cells in response to the T-independent Ag, but a significantly depressed number of PFC/10(5) spleen cells to the T-dependent Ag compared with normal B10.D2 mice and with irradiated B10.D2 recipients of syngeneic B10.D2 marrow plus spleen cells. Mice undergoing the minor Ag GvHR made significantly larger numbers of PFC/10(5) spleen cells after secondary immunization with TNP-SRBC compared with controls. In vitro assays demonstrated that B cells from mice with GvHR responded to T help from normal B10.D2 mice and that T cells from mice with GvHR provided help to normal B cells after in vivo immunization. These data demonstrate that radiation chimeras with GvHR in response to minor histocompatibility Ag have relatively normal B cell function and an apparent defect in T helper cell function that is reversible by immunization with appropriate Ag.

摘要

通过对非胸腺依赖性抗原三硝基苯-流产布鲁氏菌(TNP-Brucella abortus)和胸腺依赖性抗原三硝基苯-绵羊红细胞(TNP-SRBC)的空斑形成细胞(PFC)反应,评估了对次要组织相容性抗原产生移植物抗宿主反应(GvHR)的小鼠的B细胞和Th细胞功能。将来自B10.D2小鼠的骨髓加脾细胞移植到经致死性照射的B10.D2(同基因受体)或H-2d相容的BALB/c(异基因受体)中,以产生慢性形式的GvHR。异基因移植的BALB/c受体脾脏出现明显且成比例的淋巴细胞耗竭,B细胞、T细胞以及CD4⁺和CD8⁺T细胞亚群的百分比正常。与正常的B10.D2小鼠以及经照射的接受同基因B10.D2骨髓加脾细胞的B10.D2受体相比,发生GvHR的小鼠对非胸腺依赖性抗原产生的PFC/10⁵脾细胞数量正常,但对胸腺依赖性抗原产生的PFC/10⁵脾细胞数量明显减少。与对照组相比,经历次要抗原GvHR的小鼠在用TNP-SRBC二次免疫后产生的PFC/10⁵脾细胞数量明显更多。体外试验表明,发生GvHR的小鼠的B细胞对正常B10.D2小鼠的T辅助有反应,且发生GvHR的小鼠的T细胞在体内免疫后能为正常B细胞提供辅助。这些数据表明,对次要组织相容性抗原产生GvHR的辐射嵌合体具有相对正常的B细胞功能,以及T辅助细胞功能的明显缺陷,该缺陷可通过用适当抗原免疫来逆转。

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