Reduced frequencies of polyfunctional CMV-specific T cell responses in infants with congenital CMV infection.
Reduced frequencies of polyfunctional CMV-specific T cell responses in infants with congenital CMV infection.
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DOI：
10.1007/s10875-015-0139-3
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发表时间：
2015-04
影响因子：
9.1
通讯作者：
Luzuriaga, Katherine
中科院分区：
文献类型：
--
作者：
Gibson, Laura;Barysauskas, Constance M.;McManus, Margaret;Dooley, Sheryl;Lilleri, Daniele;Fisher, Donna;Srivastava, Tumul;Diamond, Don J.;Luzuriaga, Katherine
CMV感染仍然是疫苗开发的优先事项。婴儿接种疫苗可以改变先天性感染，并提供终身免疫。CMV特异性T细胞与控制病毒复制在早期的生命尚未完全defined. MethodsCMV特异性的CD 4和CD 8 T细胞反应进行了研究先天性CMV感染的婴儿，并与成人原发性或慢性感染。用UL 83（pp 65）或UL 122（IE-2）肽池刺激PBMC，然后用T细胞亚群（CD 4或CD 8）、表型（CD 45 RA、CCR 7）或功能（MIP 1 β、CD 107、IFNγ、IL 2）标记物的抗体染色进行流式细胞术分析。应答细胞在成人中主要是效应记忆（EM，CD 45 RA-CCR 7-），但在婴儿中是混合记忆亚群。CMV pp 65特异性CD 8 T细胞的检测在两组之间没有差异，但婴儿的总应答细胞和MIP 1 β或CD 107表达细胞的频率较低。所有组中的应答细胞为EM或效应记忆RA（CD 45 RA + CCR 7-）。多功能T细胞在婴儿中比成人更少被检测到。在成人中检测到对IE-2的反应，但在婴儿中未检测到。所有的婴儿在最初的研究（与60%的成人原发性感染），尽管CMV infection.ConclusionsReduced频率和CMV特异性的CD 4和CD 8 T细胞反应的功能改变的轮廓检测在婴儿相比，成人，并与持续CMV DNA在外周血中。
PurposeCMV infection remains a priority for vaccine development. Vaccination of infants could modify congenital infection and provide lifetime immunity. Properties of CMV-specific T cells associated with control of viral replication in early life have not been fully defined.MethodsCMV-specific CD4 and CD8 T cell responses were investigated in infants with congenital CMV infection and compared to adults with primary or chronic infection. PBMC were stimulated with UL83 (pp65) or UL122 (IE-2) peptide pools then stained with antibodies to markers of T cell subset (CD4 or CD8), phenotype (CD45RA, CCR7), or function (MIP1β, CD107, IFNγ, IL2) for flow cytometry analysis.ResultsDetection of CMV pp65-specific CD4 T cells was less common in infants than adults. Responder cells were primarily effector memory (EM, CD45RA-CCR7-) in adults, but mixed memory subsets in infants. Detection of CMV pp65-specific CD8 T cells did not differ between the groups, but infants had lower frequencies of total responding cells and of MIP1β- or CD107-expressing cells. Responder cells were EM or effector memory RA (CD45RA + CCR7-) in all groups. Polyfunctional T cells were less commonly detected in infants than adults. Responses to IE-2 were detected in adults but not infants. All infants had detectable circulating CMV DNA at initial study (versus 60 % of adults with primary infection) despite longer duration of CMV infection.ConclusionsReduced frequencies and altered functional profile of CMV-specific CD4 and CD8 T cell responses were detected in infants compared to adults, and were associated with persistent CMV DNA in peripheral blood.
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