Lack of CD4(+) T Cells Does Not Affect Induction of CD8(+) T-Cell Immunity against Encephalitozoon cuniculi Infection

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 × 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 × 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 × 10(4) in CD4(−/−) mice versus 1/3 × 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.

已有研究表明，细胞介导免疫（cell-mediated immunity）在抗兔脑炎微孢子虫（Encephalitozoon cuniculi）感染的宿主防御中发挥关键作用。本实验室既往研究已证实，细胞毒性CD8阳性T淋巴细胞（cytotoxic CD8(+) T lymphocytes, CTL）对兔脑炎微孢子虫感染小鼠的存活具有重要意义。本研究评估了CD4阳性T细胞缺陷小鼠在兔脑炎微孢子虫感染后的免疫应答情况。
与具有抗性的野生型动物一致，CD4敲除（CD4(−/−)）小鼠即便在极高感染剂量（5 × 10^7 孢子/小鼠）下，仍可清除兔脑炎微孢子虫感染。与亲代野生型小鼠相比，感染的CD4敲除小鼠的组织中未出现更高的寄生虫负荷。
与之相反，感染后第21天，易感的CD8敲除（CD8(−/−)）小鼠肝脏内的寄生虫数量较野生型对照小鼠高10^14倍。本研究还探究了CD4敲除小鼠体内针对兔脑炎微孢子虫感染的CD8阳性T细胞应答诱导过程。值得注意的是，CD4敲除小鼠可产生正常的抗原特异性CD8阳性T细胞应答（前体增殖频率为1/2.5 × 10^4，野生型对照为1/10^4）。CD4阳性T细胞缺失并未改变抗原特异性CTL应答的强度（CTL前体频率：CD4敲除小鼠为1/1.4 × 10^4，对照小鼠为1/3 × 10^4）。
将来自CD4敲除小鼠与野生型动物的免疫性CD8阳性T细胞过继转移至CD8敲除小鼠体内，均可避免其死亡。综上，兔脑炎微孢子虫感染为一类胞内寄生虫感染提供了范例：在CD4阳性T细胞缺失的情况下，仍可诱导CD8阳性T细胞免疫应答。