Moretto M, Casciotti L, Durell B, Khan I A
Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
Infect Immun. 2000 Nov;68(11):6223-32. doi: 10.1128/IAI.68.11.6223-6232.2000.
Cell-mediated immunity has been reported to play an important role in defense against Encephalitozoon cuniculi infection. Previous studies from our laboratory have underlined the importance of cytotoxic CD8(+) T lymphocytes (CTL) in survival of mice infected with E. cuniculi. In the present study, immune response against E. cuniculi infection in CD4(+) T-cell-deficient mice was evaluated. Similar to resistant wild-type animals, CD4(-/-) mice were able to resolve E. cuniculi infection even at a very high challenge dose (5 x 10(7) spores/mouse). Tissues from infected CD4(-/-) mice did not exhibit higher parasite loads in comparison to the parental wild-type mice. Conversely, at day 21 postinfection, susceptible CD8(-/-) mice had 10(14) times more parasites in the liver compared to control wild-type mice. Induction of the CD8(+) T-cell response in CD4(-/-) mice against E. cuniculi infection was studied. Interestingly, a normal antigen-specific CD8(+) T-cell response to E. cuniculi infection was observed in CD4(-/-) mice (precursor proliferation frequency, 1/2.5 x 10(4) versus 1/10(4) in wild-type controls). Lack of CD4(+) T cells did not alter the magnitude of the antigen-specific CTL response (precursor CTL frequency; 1/1.4 x 10(4) in CD4(-/-) mice versus 1/3 x 10(4) in control mice). Adoptive transfer of immune CD8(+) T cells from both CD4(-/-) and wild-type animals prevented the mortality in CD8(-/-) mice. E. cuniculi infection thus offers an example of an intracellular parasitic infection where CD8(+) T-cell immunity can be induced in the absence of CD4(+) T cells.
据报道,细胞介导的免疫在抵抗兔脑炎微孢子虫感染中发挥重要作用。我们实验室先前的研究强调了细胞毒性CD8(+) T淋巴细胞(CTL)在感染兔脑炎微孢子虫小鼠存活中的重要性。在本研究中,评估了CD4(+) T细胞缺陷小鼠对兔脑炎微孢子虫感染的免疫反应。与抗性野生型动物相似,CD4(-/-)小鼠即使在非常高的攻击剂量(5×10(7)个孢子/小鼠)下也能够清除兔脑炎微孢子虫感染。与亲代野生型小鼠相比,感染CD4(-/-)小鼠的组织中未表现出更高的寄生虫负荷。相反,在感染后第21天,易感的CD8(-/-)小鼠肝脏中的寄生虫数量比对照野生型小鼠多10(14)倍。研究了CD4(-/-)小鼠中针对兔脑炎微孢子虫感染的CD8(+) T细胞反应的诱导情况。有趣的是,在CD4(-/-)小鼠中观察到了对兔脑炎微孢子虫感染正常的抗原特异性CD8(+) T细胞反应(前体增殖频率,野生型对照为1/10(4),CD4(-/-)小鼠为1/2.5×10(4))。CD4(+) T细胞的缺乏并未改变抗原特异性CTL反应的强度(前体CTL频率;CD4(-/-)小鼠为1/1.4×10(4),对照小鼠为1/3×10(4))。来自CD4(-/-)和野生型动物的免疫CD8(+) T细胞的过继转移可预防CD8(-/-)小鼠的死亡。因此,兔脑炎微孢子虫感染提供了一个细胞内寄生虫感染的例子,即在没有CD4(+) T细胞的情况下也可诱导CD8(+) T细胞免疫。