Eradication of Cryptosporidium parvum infection by mice with ovalbumin-specific T cells.
Eradication of Cryptosporidium parvum infection by mice with ovalbumin-specific T cells.
复制标题
用卵清蛋白特异性 T 细胞根除小鼠的小隐孢子虫感染。
DOI：
10.1128/iai.68.5.2663-2670.2000
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发表时间：
2000
影响因子：
3.1
通讯作者：
Hayward,A
中科院分区：
文献类型：
--
作者：
Lukin,K;Cosyns,M;Mitchell,T;Saffry,M;Hayward,A
CD 154是小鼠清除微小隐孢子虫感染所必需的，但这种配体是否必须在T细胞上表达才具有对C. parvum尚未确定。我们感染了DO11.10（卵清蛋白特异性）T细胞受体转基因小鼠，这些小鼠已经被C. parvumand发现感染在6周内被清除，而RAG−/−对照不能清除C。细小病毒感染恢复伴随着脾T细胞数量的增加，具有CD 44 high表型，这是记忆细胞的特征。以确定是否aC。感染的环境足以激活转基因T细胞，我们重建了C.用DO11.10 RAG−/−脾细胞感染细小病毒的BALB/c SCID小鼠。粪便排泄的C.在过继转移后的12周内，除非小鼠也注射耐受剂量的卵清蛋白，否则parvumantigen的作用停止。DO11.10 T细胞主要分布于C.在注射后48小时内，感染细小病毒但未感染的BALB/c SCID宿主。转染的DO11.10细胞在C.感染了细小病毒但未感染的受体。来自CD 154敲除供体的DO11.10脾细胞未能清除aC。细小病毒感染，证实恢复期需要CD 154。在体外，DO11.10细胞对C. tBlast基因库检索显示卵清蛋白肽与C. parvumDNA序列。给予带有李斯特菌特异性转基因的RAG−/− CD 8 +T细胞的细小病毒感染的SCID小鼠没有从C.细小病毒感染我们的数据表明，抗原非特异性CD 4 + T细胞效应机制与免疫系统的先天性臂相结合足以根除C。细小病毒感染
CD154 is necessary for mice to clear aCryptosporidium parvuminfection, but whether this ligand has to be expressed on T cells with specificity forC. parvumhas not been determined. We infected DO11.10 (ovalbumin specific) T-cell receptor transgenic mice that had been bred to a RAG−/−background withC. parvumand found that the infection was cleared within 6 weeks, while RAG−/−controls were unable to clearC. parvuminfection. Recovery was accompanied by an increase in the number of splenic T cells with the CD44highphenotype that characterizes memory cells. To determine whether aC. parvum-infected environment sufficed to activate transgenic T cells, we reconstitutedC. parvum-infected BALB/c SCID mice with DO11.10 RAG−/−splenocytes. Fecal excretion ofC. parvumantigen ceased in the 12 weeks following the adoptive transfer, unless the mice were also injected with tolerizing doses of ovalbumin. DO11.10 T cells were found in the submucosa ofC. parvum-infected, but not uninfected, BALB/c SCID hosts within 48 h of injection. The transferred DO11.10 T cells divided and acquired a CD44highmemory phenotype inC. parvum-infected, but not uninfected, recipients. DO11.10 splenocytes from CD154 knockout donors failed to clear aC. parvuminfection, confirming a requirement for CD154 in recovery. In vitro, the DO11.10 cells did not proliferate in response toC. parvumantigen, and a tBlast GenBank search revealed no matches between the ovalbumin peptide andC. parvumDNA sequences.C. parvum-infected SCID mice given RAG−/−CD8+T cells with aListeria-specific transgene did not recover fromC. parvuminfection. Our data suggest that antigen-nonspecific CD4+T-cell effector mechanisms in combination with the innate arm of the immune system are sufficient for the eradication ofC. parvuminfection.