Protection against Pneumocystis carinii pneumonia by antibodies generated from either T helper 1 or T helper 2 responses
Protection against Pneumocystis carinii pneumonia by antibodies generated from either T helper 1 or T helper 2 responses
复制标题
DOI：
10.1128/iai.65.12.5052-5056.1997
复制
发表时间：
1997-12-01
影响因子：
3.1
通讯作者：
Harmsen, AG
中科院分区：
文献类型：
--
作者：
Garvy, BA;Wiley, JA;Harmsen, AG
为了确定与辅助性T细胞1（Th 1）或Th 2应答相关的不同抗体同种型是否对卡氏肺孢子虫具有保护作用，（IL-4（-/-）小鼠）或γ干扰素基因（IFN-γ（-/-）小鼠）沿着野生型C57 BL/6小鼠一起进行针对卡氏肺孢子虫的免疫接种，通过使用单克隆抗体在体内耗尽T细胞，用10（7）个活的卡氏肺孢子虫生物体进行肠内再攻击，几乎所有免疫小鼠在攻击的21天内解决了它们的肺卡氏肺孢子虫感染（检测限，log（10）4.06），即使它们耗尽了T细胞。在卡氏疟原虫攻击后第21天，耗尽T细胞的未免疫小鼠具有显著的肺部感染（>log（10）5.5）。IFN-γ（-/-）和野生型小鼠产生卡氏肺孢子虫特异性免疫球蛋白，主要是免疫球蛋白G1（IgG 1）亚类，血清中卡氏肺孢子虫特异性IgG 2a、IgG 2b或IgG 3相对较少，这是Th 2型应答的特征。相比之下，IL-4（-/-）小鼠的血清中主要有IgG 2b卡氏肺孢子虫特异性抗体应答，IgG 1非常少。虽然IgG 2b在IL-4（-/-）小鼠中是主要同种型，但IgG 2a和IgG 3在这些小鼠中的光密度值显著较高（分别是IFN-γ（-/-）小鼠的2倍和3倍），这是Th 1型应答的特征。这些数据表明卡氏肺孢子虫感染的消退可由特异性抗体应答介导主要是Th 1或Th 2型。此外，尽管野生型小鼠产生了Th 2样抗体反应，但IL-4（-/-）小鼠可以解决卡氏肺孢子虫肺炎，这表明在缺乏IL-4的情况下可能会出现对卡氏肺孢子虫的耐药性。
To determine whether different antibody isotypes associated with T helper 1 (Th1) or Th2 responses are protective against Pneumocystis carinii, mice with disrupted interleukin 4 genes (IL-4(-/-) mice) or gamma interferon genes (IFN-gamma(-/-) mice) along with wild-type C57BL/6 mice were immunized intratracheally against P. carinii, depleted of T cells in vivo by use of monoclonal antibodies, and rechallenged intratracheally with 10(7) viable P. carinii organisms, Nearly all immunized mice resolved their lung P. carinii infections (limit of detection, log(10) 4.06) within 21 days of challenge even though they were depleted of T cells. Unimmunized mice depleted of T cells had significant lung infections (>log(10) 5.5) at day 21 post-P. carinii challenge. IFN-gamma(-/-) and wild-type mice developed P. carinii-specific immunoglobulin primarily of the immunoglobulin G1 (IgG1) subclass with relatively little P. carinii-specific IgG2a, IgG2b, or IgG3 in their sera, characteristic of a Th2-type response. In contrast, IL-4(-/-) mice had primarily an IgG2b P. carinii-specific antibody response in their sera with very little IgG1. Although IgG2b was the predominant isotype in IL-4(-/-) mice, optical density values of IgG2a and IgG3 were significantly higher in these mice (two and three times, respectively) than in IFN-gamma(-/-) mice, characteristic of a Th1-type response, Together, these data indicate that resolution of P. carinii infection can be mediated by specific antibody responses and that the antibody response can be either a predominantly Th1 or Th2 type. Furthermore, although wild-type mice mounted a Th2-like antibody response, IL-4(-/-) mice could resolve P. carinii pneumonia, indicating that resistance to P. carinii can occur in the absence of IL-4.