Sasaki Y, Darmochwal-Kolarz D, Suzuki D, Sakai M, Ito M, Shima T, Shiozaki A, Rolinski J, Saito S
Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan.
Clin Exp Immunol. 2007 Jul;149(1):139-45. doi: 10.1111/j.1365-2249.2007.03397.x. Epub 2007 Apr 25.
CD4(+) CD25(bright) regulatory T (T(reg)) cells have been identified as a principle regulator of tolerance during pregnancy. In the setting of pre-eclampsia, however, little is known about the dynamics of these cells. In the current study, we determined CD4(+) CD25(bright) T(reg) cells in the peripheral blood using flow cytometry and forkhead box P3 (FoxP3(+)) cells at the placental bed using immunohistochemical staining. Peripheral blood mononuclear cells (PBMC) of 38 pre-eclamptic cases (17 cases Japanese, 21 cases Polish), 40 normal late pregnancy subjects (20 subjects Japanese, 20 subjects Polish), and 21 non-pregnant healthy controls (10 subjects Japanese, 11 subjects Polish) were included. We found the percentage of CD25(bright) cells within the CD4(+) T cell population in PBMC was reduced significantly in both Japanese and Polish pre-eclamptic cases than in normal pregnancy subjects (P < 0.001) and non-pregnant healthy controls (P < 0.001). Also, the percentage of FoxP3(+) cells within CD3(+) T cells in the placental bed biopsy samples of pre-eclamptic cases were decreased compared to those in normal pregnancy subjects. These findings suggest that a decreased number of T(reg) cells was present in pre-eclampsia, and these changes might break the maternal tolerance to the fetus.
CD4(+)CD25(bright)调节性T(T(reg))细胞已被确定为孕期免疫耐受的主要调节因子。然而,在子痫前期的情况下,对这些细胞的动态变化知之甚少。在本研究中,我们使用流式细胞术测定外周血中的CD4(+)CD25(bright)T(reg)细胞,并使用免疫组织化学染色法测定胎盘床处的叉头框P3(FoxP3(+))细胞。纳入了38例子痫前期病例(17例日本病例,21例波兰病例)、40例正常妊娠晚期受试者(20例日本受试者,20例波兰受试者)和21例非妊娠健康对照者(10例日本受试者,11例波兰受试者)的外周血单个核细胞(PBMC)。我们发现,日本和波兰子痫前期病例的PBMC中CD4(+)T细胞群体内CD25(bright)细胞的百分比均显著低于正常妊娠受试者(P<0.001)和非妊娠健康对照者(P<0.001)。此外,子痫前期病例胎盘床活检样本中CD3(+)T细胞内FoxP3(+)细胞的百分比与正常妊娠受试者相比有所降低。这些发现表明子痫前期存在T(reg)细胞数量减少的情况,并且这些变化可能会打破母体对胎儿的免疫耐受。