Ovsyannikova Inna G, Jacobson Robert M, Ryan Jenna E, Vierkant Robert A, Pankratz V Shane, Jacobsen Steven J, Poland Gregory A
Mayo Vaccine Research Group, Mayo Clinic and Foundation, Guggenheim 611C, 200 1st Street SW, Rochester, MN 55905, USA.
Immunogenetics. 2005 Feb;56(11):798-807. doi: 10.1007/s00251-004-0756-0. Epub 2005 Jan 27.
Measles virus-specific T cells and the production of cytokines play a critical role in the immune response following measles immunization. To understand the genetic factors that influence variation in IFN-gamma and IL-4 responses following measles immunization and to provide insight into the factors influencing both cellular and humoral immunity to measles, we assessed associations between human leukocyte antigen (HLA) class II genes and measles-specific Th1 and Th2-type cytokine responses in peripheral blood lymphocytes from 339 children previously vaccinated with two doses of measles-mumps-rubella vaccine (MMR-II). Median values for measles-specific IFN-gamma and IL-4 secretion levels were 40.73 and 9.71 pg/ml, respectively. The global tests suggested associations between measles-specific IFN-gamma response and alleles of the DRB1 and DQB1 loci (P=0.07 and P=0.02, respectively). Specifically, DRB1*0301, *0901, and 1501 alleles were significantly associated with IFN-gamma secretion. The alleles that suggested evidence of an HLA association with IL-4 secretion were DRB10103, *0701, and 1101. Th1 cytokine responses and DQB1 allele associations revealed that the alleles with the strongest association with IFN-gamma secretion were DQB10201, *0303, *0402, and 0602. Specific alleles with a suggestive association with low measles-specific Th2 cytokine responses were DQB10202 and 0503. In addition, DPB10101, *0201, and 0601 alleles provided suggestive evidence of an HLA association with measles-induced IFN-gamma response, while DPB10501 was associated with an IL-4 response. These data suggest that IFN-gamma and IL-4 cytokine responses to measles may be genetically restricted in part by HLA class II genes, which in turn can restrict the cellular immune response to measles vaccine.
麻疹病毒特异性T细胞和细胞因子的产生在麻疹免疫后的免疫反应中起关键作用。为了解影响麻疹免疫后IFN-γ和IL-4反应变异的遗传因素，并深入了解影响麻疹细胞免疫和体液免疫的因素，我们评估了339名先前接种两剂麻疹-腮腺炎-风疹疫苗（MMR-II）的儿童外周血淋巴细胞中人类白细胞抗原（HLA）II类基因与麻疹特异性Th1和Th2型细胞因子反应之间的关联。麻疹特异性IFN-γ和IL-4分泌水平的中位数分别为40.73和9.71 pg/ml。整体检验表明麻疹特异性IFN-γ反应与DRB1和DQB1位点的等位基因之间存在关联（P分别为0.07和0.02）。具体而言，DRB10301、0901和1501等位基因与IFN-γ分泌显著相关。提示HLA与IL-4分泌相关的等位基因是DRB10103、0701和1101。Th1细胞因子反应与DQB1等位基因的关联表明，与IFN-γ分泌关联最强的等位基因是DQB10201、0303、0402和0602。与低麻疹特异性Th2细胞因子反应存在提示性关联的特定等位基因是DQB10202和0503。此外，DPB10101、0201和0601等位基因提供了HLA与麻疹诱导的IFN-γ反应相关的提示性证据，而DPB10501与IL-4反应相关。这些数据表明，对麻疹的IFN-γ和IL-4细胞因子反应可能部分受到HLA II类基因的遗传限制，这反过来又可能限制对麻疹疫苗的细胞免疫反应。
