Villegas E N, Elloso M M, Reichmann G, Peach R, Hunter C A
Department of Pathobiology, University of Pennsylvania, Philadelphia 19104, USA.
J Immunol. 1999 Sep 15;163(6):3344-53.
CD28 deficient (CD28-/-) mice were used to study the role of costimulation in the T cell-mediated, IFN-gamma-dependent mechanism of resistance to Toxoplasma gondii. These mice were resistant to infection with the ME49 strain of T. gondii. Analysis of the immune response of acutely infected CD28-/- mice revealed that IL-12 was required for T cell production of IFN-gamma and this was independent of the CD40/CD40 ligand interaction. A similar mechanism of IL-12-dependent, CD28/B7 independent production of IFN-gamma by T cells was also observed in wild-type mice. Interestingly, although chronically infected wild-type mice were resistant to rechallenge with the virulent RH strain of T. gondii, chronically infected CD28-/- mice were susceptible to rechallenge with the RH strain. This deficiency in the protective memory response by CD28-/- mice correlated with a lack of IL-2 and IFN-gamma in recall responses and reduced numbers of CD4+ T cells expressing a memory phenotype. Together, our findings demonstrate that CD28 is not required for the development of a protective T cell response to T. gondii, but CD28 is required for an optimal secondary immune response.
利用CD28缺陷（CD28-/-）小鼠研究共刺激在T细胞介导的、依赖干扰素-γ的抗刚地弓形虫机制中的作用。这些小鼠对刚地弓形虫ME49株感染具有抗性。对急性感染的CD28-/-小鼠的免疫反应分析表明，T细胞产生干扰素-γ需要白细胞介素-12，且这一过程独立于CD40/CD40配体相互作用。在野生型小鼠中也观察到了T细胞依赖白细胞介素-12、不依赖CD28/B7产生干扰素-γ的类似机制。有趣的是，虽然慢性感染的野生型小鼠对刚地弓形虫强毒株RH株的再次攻击具有抗性，但慢性感染的CD28-/-小鼠对RH株的再次攻击敏感。CD28-/-小鼠保护性记忆反应的这种缺陷与回忆反应中白细胞介素-2和干扰素-γ的缺乏以及表达记忆表型的CD4+ T细胞数量减少相关。总之，我们的研究结果表明，CD28对于对刚地弓形虫产生保护性T细胞反应并非必需，但对于最佳的二次免疫反应是必需的。
