Granzyme B mediated function of Parvovirus B19-specific CD4(+) T cells.
Granzyme B mediated function of Parvovirus B19-specific CD4(+) T cells.
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DOI：
10.1038/cti.2015.13
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发表时间：
2015-07
影响因子：
5.8
通讯作者：
Franssila R
中科院分区：
文献类型：
--
作者：
Kumar A;Perdomo MF;Kantele A;Hedman L;Hedman K;Franssila R
具有细胞溶解潜能的CD 4 + T细胞（CD 4 + CTL）的新概念正在出现。这些细胞似乎在控制恶性肿瘤和慢性感染方面发挥了作用。人细小病毒B19可引起持续性感染，但没有关于B19特异性CD 4 + CTL存在的数据。这些细胞可能在一些据报道与B19相关的自身免疫性疾病的发病机制中发挥作用。我们通过用重组B19-VP 2病毒样颗粒刺激外周血单个核细胞（PBMC）来探索人细小病毒B19特异性T细胞的细胞溶解潜力。通过基于酶免疫测定的组织培养上清液中颗粒酶B（GrB）和穿孔素的定量、细胞内细胞因子染色（ICS）和检测直接细胞毒性来确定细胞溶解潜力。GrB和穿孔素与B19抗原的反应在B19血清阳性个体中很容易检测到。T细胞耗竭、HLA阻断和ICS实验表明GrB和穿孔素由CD 4 + T细胞分泌。发现具有强GrB应答的CD 4 + T细胞表现出直接的细胞毒性。如预期的，B19特异性CD 4 + T细胞的ICS显示出预期的GrB、穿孔素和干扰素γ（IFN-γ）的共表达。出乎意料的是，还检测到GrB和白细胞介素17（IL-17）的强共表达。这些细胞表达自然杀伤（NK）细胞表面标志物CD 56以及CD 4表面标志物。据我们所知，这是第一个关于共表达CD 56抗原的病毒特异性CD 4 + CTL的报道。我们的研究结果表明，在B19免疫的CD 4 + CTL的作用。这些细胞可以在免疫调节和触发自身免疫现象（如系统性红斑狼疮（SLE）或类风湿性关节炎）中起作用。
A novel conception of CD4+ T cells with cytolytic potential (CD4+ CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4+ CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles. The cytolytic potential was determined by enzyme immunoassay-based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19-seropositive individuals. T-cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4+ T cells. CD4+ T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19-specific CD4+ T cells showed expected co-expression of GrB, perforin and interferon gamma (IFN-γ). Unexpectedly, also a strong co-expression of GrB and interleukin 17 (IL-17) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus-specific CD4+ CTLs co-expressing CD56 antigen. Our results suggest a role for CD4+ CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis.