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原发性感染孕妇和既往感染对照受试者针对人巨细胞病毒(HCMV)蛋白的不同抗原特异性CD4和CD8 T细胞反应。

Different Antigen-Specific CD4 and CD8 T-Cell Response against HCMV Proteins in Pregnant Women with Primary Infection and in Control Subjects with Remote Infection.

作者信息

Zavaglio Federica, d'Angelo Piera, Fornara Chiara, Zelini Paola, Comolli Giuditta, Furione Milena, Arossa Alessia, Spinillo Arsenio, Lilleri Daniele, Baldanti Fausto

机构信息

Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.

General Clinical Laboratory, with Specialist Areas of Clinical Pathology, Microbiology and Virology, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy.

出版信息

J Clin Med. 2024 Sep 13;13(18):5448. doi: 10.3390/jcm13185448.

Abstract

: Human cytomegalovirus (HCMV) is the most frequent cause of congenital infections. The HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection in pregnancy. In this study, the antigen-specific T-cell response against different HCMV proteins (IE-1, pp65, gB, gHgLpUL128L) was investigated in pregnant women with primary infection and in control subjects with remote infection to identify possible components of a vaccine. : Blood samples from 35 pregnant women with HCMV primary infection and 30 HCMV-seropositive healthy adult subjects with remote infection were tested. The antigen-specific T-cell response was measured using cytokine intracellular staining after stimulation with IE-1, pp65, gB and gHgLpUL128L peptides pool. : The pp65-specific CD4 T-cell response was higher in pregnant women with HCMV primary infection at the late time point and in control subjects with remote infection, while the pregnant women at the early time point showed a higher gB-specific CD8 T-cell response. Regarding the CD4 and CD8 T-cell phenotypes, we observed that HCMV-specific CD4 and CD8 T cells expressing CD45RA remained constant in pregnant women with primary infection at the early and late time points and in subjects with remote infection, while HCMV-specific CD4 and CD8 T cells expressing IL-7R or producing IL-2 were higher in control subjects with remote infection than in pregnant women with HCMV primary infection. : The T-cell response was higher against gB in the early phase of infection and against pp65 in the late phase. Therefore, these proteins should be taken into consideration as candidates for a vaccine.

摘要

人类巨细胞病毒(HCMV)是先天性感染最常见的病因。原发性感染中HCMV特异性T细胞反应可能有助于确定孕期免疫保护的可靠相关因素。在本研究中,调查了原发性感染孕妇和既往感染对照者针对不同HCMV蛋白(IE-1、pp65、gB、gHgLpUL128L)的抗原特异性T细胞反应,以确定疫苗可能的组成成分。

检测了35例原发性感染HCMV的孕妇和30例既往感染HCMV的血清学阳性健康成年对照者的血样。用IE-1、pp65、gB和gHgLpUL128L肽池刺激后,通过细胞内细胞因子染色测量抗原特异性T细胞反应。

在晚期原发性感染HCMV的孕妇和既往感染对照者中,pp65特异性CD4 T细胞反应较高,而早期孕妇则表现出较高的gB特异性CD8 T细胞反应。关于CD4和CD8 T细胞表型,我们观察到,在原发性感染的早期和晚期孕妇以及既往感染的受试者中,表达CD45RA的HCMV特异性CD4和CD8 T细胞保持恒定,而表达IL-7R或产生IL-2的HCMV特异性CD4和CD8 T细胞在既往感染对照者中高于原发性感染HCMV的孕妇。

感染早期针对gB的T细胞反应较高,晚期针对pp65的反应较高。因此,这些蛋白应被视为疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4c5/11432261/bc0f0c54230f/jcm-13-05448-g001.jpg

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