WASP- mice exhibit defective immune responses to influenza A virus, Streptococcus pneumoniae, and Mycobacterium bovis BCG
WASP- mice exhibit defective immune responses to influenza A virus, Streptococcus pneumoniae, and Mycobacterium bovis BCG
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DOI：
10.1016/j.exphem.2004.12.006
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发表时间：
2005-04-01
影响因子：
2.6
通讯作者：
Strom, TS
中科院分区：
文献类型：
--
作者：
Andreansky, S;Liu, HY;Strom, TS
Objective.为了定量WASP（-）小鼠对三种不同病原体的免疫应答：A型流感病毒、肺炎链球菌和牛分枝杆菌。通过四聚体测定定量了对甲型流感病毒的初级和次级T细胞反应。还测量了肺的病毒清除率。鼻内接种发光沙门氏菌的致死率。通过剂量递增和直接发光成像评估肺炎链球菌感染。静脉接种M.牛，肺，肝，脾中残留分枝杆菌用标准培养方法测定。对甲型流感病毒的继发性T细胞应答降低与脾T和B细胞的相对但非绝对损失相关，与临床Wiskott-Aldrich综合征（WAS）中观察到的相似，以及病毒从肺中清除较慢。继发性T细胞应答的降低幅度与初次接种后流感特异性T细胞的进行性损失相关。WASP-小鼠鼻内接种沙门氏菌后对致死性肺炎的易感性增加。肺炎，这是WAS患者临床并发症的最常见原因之一。WASP-小鼠清除M.牛卡介苗（BCG）从肺、肝和脾中排出的速度较慢。然而，骨髓来源的巨噬细胞显示出正常的响应于M. bovis.Conclusions.这些结果表明，WASP-小鼠在三种不同的病原体方面是功能性免疫缺陷的，并提供了相关的终点，在这个模型中的治疗方式的研究。他们还提出了一个特定的生理机制，未能积累记忆T细胞，至少有一个缺陷的免疫反应。(c)2005年国际实验血液学学会。爱思唯尔公司出版
Objective. To quantify the immune response of WASP(-) mice to three different pathogens: influenza A virus, Streptococcus pneumoniae, and Mycobacterium bovis.Methods. Primary and secondary T-cell responses to influenza A virus were quantified via tetramer assays. Viral clearance from lung was also measured. Lethality of intranasal inoculation with luminescent S. pneumoniae was assessed by dose escalation and direct luminescence imaging. After intravenous inoculation with M. bovis, residual mycobacteria in lung, liver, and spleen were measured by standard culture methods.Results. The reduced secondary T-cell response to influenza A virus correlates with a relative but not absolute loss of splenic T and B cells similar to that seen in clinical Wiskott-Aldrich Syndrome (WAS), and slower clearance of virus from lung. The reduced magnitude of the secondary T-cell response correlates with a progressive loss of influenza-specific T cells after primary inoculation. WASP- mice show an increased susceptibility to lethal pneumonia after intranasal inoculation with S. pneumoniae, which is among the most frequent causes of clinical complications in WAS patients. WASP- mice clear M. bovis bacille Calmette-Guerin (BCG) more slowly from lung, liver, and spleen. Bone marrow-derived macrophages, however, show normal ex vivo cytokine secretion in response to M. bovis.Conclusions. These results demonstrate that WASP- mice are functionally immunodeficient in regard to three different pathogens, and provide relevant end points for the study of treatment modalities in this model. They also suggest a specific physiologic mechanism, failure to accumulate memory T cells, for at least one of the defective immune responses. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc.