Wagner Claudia S, Walther-Jallow Lilian, Buentke Eva, Ljunggren Hans-Gustaf, Achour Adnane, Chambers Benedict J
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
J Leukoc Biol. 2008 Jan;83(1):56-63. doi: 10.1189/jlb.0307181. Epub 2007 Sep 26.
Human cytomegalovirus (HCMV) encodes the MHC class I-like molecule UL18, which binds with high affinity to the leukocyte Ig-like receptor-1 (LIR-1), an inhibitory receptor commonly expressed on myeloid cells and subsets of NK and T cells. The exact role of UL18 is not known, in particular in relation to its proposed role in HCMV immune escape. Given the ubiquitous expression of LIR-1 on dendritic cells (DCs), we hypothesized that UL18 may affect DC function. To study the effects of UL18 on DC, we made use of UL18 fusion proteins. We demonstrate that UL18 fusion proteins inhibit the chemotaxis of DCs. Furthermore, UL18 interfered with CD40 ligand-induced maturation of DCs, resulting in reduced allogeneic T cell proliferation. Finally, we demonstrate that UL18 proteins up-regulate the expression of the maturation marker CD83 on immature monocyte-derived DCs and induce cytokine production. The capacity of UL18 to affect the function and the phenotype of DCs suggests a novel role for this HCMV-derived protein.
人巨细胞病毒（HCMV）编码I类主要组织相容性复合体（MHC）样分子UL18，它与白细胞免疫球蛋白样受体-1（LIR-1）高亲和力结合，LIR-1是一种抑制性受体，通常在髓样细胞以及自然杀伤细胞和T细胞亚群上表达。UL18的确切作用尚不清楚，特别是与其在HCMV免疫逃逸中所起的假定作用相关的方面。鉴于LIR-1在树突状细胞（DC）上普遍表达，我们推测UL18可能会影响DC的功能。为了研究UL18对DC的影响，我们使用了UL18融合蛋白。我们证明UL18融合蛋白可抑制DC的趋化作用。此外，UL18干扰CD40配体诱导的DC成熟，导致同种异体T细胞增殖减少。最后，我们证明UL18蛋白可上调未成熟单核细胞来源的DC上成熟标志物CD83的表达并诱导细胞因子产生。UL18影响DC功能和表型的能力表明这种源自HCMV的蛋白具有新的作用。
