Holmes B J, Diaz-Sanchez D, Lawrence R A, Bell E B, Maizels R M, Kemeny D M
Department of Immunology, King's College School of Medicine and Dentistry, London, UK.
Immunology. 1996 Jun;88(2):252-60. doi: 10.1111/j.1365-2567.1996.tb00012.x.
Recent data have indicated that CD8+ T cells suppress rodent IgE responses. In this study we investigated the effect of CD8+ T cells on primary and established IgE responses in euthymic and athymic nude rats. Euthymic PVG rats were depleted of CD8+ T cells by intraperitoneal injection of a CD8-specific monoclonal antibody (OX8), which resulted in an apparent loss of 92% of splenic and 98% of peripheral blood CD8+ T cells. The CD8+ T-cell depleted animals failed to mount a significant IgE response compared with control animals given an irrelevant monoclonal antibody (OX21). Furthermore, PVG nude rats reconstituted with purified CD4+ thoracic duct lymphocytes (TDL) alone failed to mount a significant IgE response, while animals given unfractionated TDL (containing CD4+ and CD8+ T cells) did. Depletion of CD8+ T cells 7 days prior to immunization and subsequent reconstitution at the time of immunization restored the IgE response. In contrast, removal of CD8+ T cells 1 month after induction of IgE by immunization with ovalbumin (OVA) and ricin prolonged the IgE response. In all cases IgG antibody responses were unaffected by the presence or absence of CD8+ T cells. This study shows that some CD8+ T cells are required for IgE, but not IgG, production to soluble antigen in a primary immune response. However, later in the immune response CD8+ T cells were shown to inhibit IgE production. These effects were apparently restricted to the immune response to soluble antigen, as Hooded Lister rats infected with 9000 larvae of the nematode Nippostrongylus brasiliensis produced high sustained levels of circulating IgE, in excess of 10 micrograms/ml, regardless of whether CD8+ T cells were depleted before or 1 month after infection.
近期数据表明,CD8⁺ T细胞可抑制啮齿动物的IgE反应。在本研究中,我们调查了CD8⁺ T细胞对正常胸腺和无胸腺裸鼠初次及已建立的IgE反应的影响。通过腹腔注射CD8特异性单克隆抗体(OX8)使正常胸腺的PVG大鼠的CD8⁺ T细胞耗竭,导致脾脏中92%以及外周血中98%的CD8⁺ T细胞明显缺失。与给予无关单克隆抗体(OX21)的对照动物相比,CD8⁺ T细胞耗竭的动物未能产生显著的IgE反应。此外,仅用纯化的CD4⁺胸导管淋巴细胞(TDL)重建的PVG裸鼠未能产生显著的IgE反应,而给予未分离的TDL(包含CD4⁺和CD8⁺ T细胞)的动物则产生了反应。免疫前7天耗竭CD8⁺ T细胞并在免疫时随后进行重建可恢复IgE反应。相反,在用卵清蛋白(OVA)和蓖麻毒素免疫诱导IgE 1个月后去除CD8⁺ T细胞可延长IgE反应。在所有情况下,IgG抗体反应不受CD8⁺ T细胞存在与否的影响。本研究表明,在初次免疫反应中,产生针对可溶性抗原的IgE而非IgG需要一些CD8⁺ T细胞。然而,在免疫反应后期,CD8⁺ T细胞被证明可抑制IgE产生。这些效应显然仅限于对可溶性抗原的免疫反应,因为感染了9000条巴西日圆线虫幼虫的带帽利斯特大鼠,无论在感染前还是感染后1个月耗竭CD8⁺ T细胞,都会产生持续高水平的循环IgE,超过10微克/毫升。