Ramos E L, Turka L A, Leggat J E, Wood I G, Milford E L, Carpenter C B
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Transplantation. 1989 Mar;47(3):465-71. doi: 10.1097/00007890-198903000-00013.
Two monoclonal antibodies, anti-2H4 and anti-4B4, reciprocally divide the T4+ (CD4+) and T8+ (CD8+) lymphocytes into T4+2H4+, T4+4B4+, T8+2H4+ and T8+4B4+ subsets. The T4+2H4+, T4+4B4+ and T8+2H4+ subsets possess suppressor-inducer, helper-inducer, and suppressor-effector function, respectively, as previously defined in a system of B cell immunoglobulin production. Using monoclonal antibodies, including anti-2H4 and anti-4B4, and flow cytometry, we monitored lymphocyte subpopulations in 66 renal allograft recipients. We found that patients with stable allograft function have a decrease in the percentage of total T4+ lymphocytes from 41.9 +/- 9.5% pretransplant (pre-Tx) to 36.3 +/- 13.9% posttransplant (post-Tx) (P less than 0.05). This decrease was seen mainly in the T4+4B4+ or helper-inducer subset from 20.8 +/- 4.7% (pre-Tx) to 16.0 +/- 6.3% (post-Tx) (P less than 0.005). Patients with stable function were also noted to have an increase in the percentage of total T8+ lymphocytes from 21.3 +/- 10.7% (pre-Tx) to 30.9 +/- 15.4% (post-Tx) (P less than 0.02). Examination of T8 subsets revealed that a statistically significant increase was seen in the T8+2H4+ or suppressor effector subset from 15.5 +/- 9.2% (pre-Tx) to 21.5 +/- 10.2% (post-Tx) (P less than 0.01). Additionally, serial studies on 14 patients revealed an increase in the %T4+2H4+ suppressor-inducer subset from 9.31 +/- 3.64% (pre-Tx) to 15.71 +/- 6.41% (post-Tx) (P less than 0.0025). Since the role of these subsets has not been established in alloimmunity, in vitro allogeneic studies of 2H4-enriched (2H4+) and 2H4-depleted (2H4-) lymphocytes from normal peripheral blood were performed. In the mixed lymphocyte reaction, 2H4+ cells proliferated less than 2H4- cells (cpm ratio 2H4+/2H4-: 0.63-0.84), but 2H4+ cells generated twice as much suppressor activity as 2H4- cells (ratio % suppression 2H4+/2H4-: 1.9-2.3). These results suggest that 2H4+ cells play a role in the suppressor limb of the alloimmune response and that the increase in cells of this phenotype in our transplant population may be responsible for the maintenance of stable allograft function.
两种单克隆抗体，抗-2H4和抗-4B4，将T4 +（CD4 +）和T8 +（CD8 +）淋巴细胞相互分为T4 + 2H4 +、T4 + 4B4 +、T8 + 2H4 +和T8 + 4B4 +亚群。如先前在B细胞免疫球蛋白产生系统中所定义，T4 + 2H4 +、T4 + 4B4 +和T8 + 2H4 +亚群分别具有抑制诱导、辅助诱导和抑制效应功能。使用包括抗-2H4和抗-4B4在内的单克隆抗体以及流式细胞术，我们监测了66例肾移植受者的淋巴细胞亚群。我们发现，移植肾功能稳定的患者，其总T4 +淋巴细胞百分比从移植前（Tx前）的41.9±9.5%降至移植后（Tx后）的36.3±13.9%（P<0.05）。这种下降主要见于T4 + 4B4 +或辅助诱导亚群，从20.8±4.7%（Tx前）降至16.0±6.3%（Tx后）（P<0.005）。还注意到移植肾功能稳定的患者，其总T8 +淋巴细胞百分比从21.3±10.7%（Tx前）增至30.9±15.4%（Tx后）（P<0.02）。对T8亚群的检查显示，T8 + 2H4 +或抑制效应亚群有统计学显著增加，从15.5±9.2%（Tx前）增至21.5±10.2%（Tx后）（P<0.01）。此外，对14例患者的系列研究显示，T4 + 2H4 +抑制诱导亚群的百分比从9.31±3.64%（Tx前）增至15.71±6.41%（Tx后）（P<0.0025）。由于这些亚群在同种免疫中的作用尚未确定，因此对来自正常外周血的富含2H4（2H4 +）和缺乏2H4（2H4 -）的淋巴细胞进行了体外同种异体研究。在混合淋巴细胞反应中，2H4 +细胞的增殖少于2H4 -细胞（2H4 + /2H4 -的cpm比值：0.63 - 0.84），但2H4 +细胞产生的抑制活性是2H4 -细胞的两倍（2H4 + /2H4 -的抑制百分比比值：1.9 - 2.3）。这些结果表明，2H
