Saha B, Chattopadhyay S, Germond R, Harlan D M, Perrin P J
Immune Cell Biology Program, Naval Medical Research Institute, Bethesda, USA.
Eur J Immunol. 1998 Dec;28(12):4213-20. doi: 10.1002/(SICI)1521-4141(199812)28:12<4213::AID-IMMU4213>3.0.CO;2-C.
Since both the nature and the amplitude of an antigen-specific T cell response are dependent on co-stimulatory signals, we have investigated the role of CD28/CD152-mediated T cell co-stimulation in the regulation of experimental cutaneous leishmaniasis. CD28-deficient mice and their wild-type littermates are equally susceptible to Leishmania major infection. Whole anti-CD152 antibody significantly exacerbates the disease while anti-CD152 Fab ameliorates the disease in genetically susceptible BALB/c mice but not in C57BL/6, a resistant strain. The anti-CD152-induced exacerbation of the disease is accompanied by increased IL-4-secreting cell number, diminished parasite-specific delayed-type hypersensitivity (DTH) response and augmented anti-2,4,6-trinitrophenyl (TNP) IgG1 in response to TNP-leishmanial antigen crude soluble antigen (CSA), suggesting an exaggerated Th2 type of response. Anti-CD152 Fab-mediated amelioration of the disease is associated with increased IFN-gamma-secreting cell number, increased parasite-specific DTH response and enhanced IgG2a isotype in response to TNP-CSA suggesting a Th1 type of response. Unlike TNP-CSA, TNP-keyhole limpet hemocyanin does not induce the change in Ig isotype, indicating that the immunomodulatory effect of anti-CD152 is antigen specific. Anti-CD152 antibody-induced early change in Th subsets suggests an important role for CD152 in determining the course of L. major infection, perhaps by alteration of Th subset differentiation.
由于抗原特异性T细胞应答的性质和强度均依赖于共刺激信号，我们研究了CD28/CD152介导的T细胞共刺激在实验性皮肤利什曼病调控中的作用。CD28缺陷小鼠及其野生型同窝小鼠对硕大利什曼原虫感染的易感性相同。在基因易感的BALB/c小鼠中，完整的抗CD152抗体显著加重疾病，而抗CD152 Fab片段则改善疾病，但在抗性品系C57BL/6小鼠中无此作用。抗CD152诱导的疾病加重伴随着分泌IL-4的细胞数量增加、寄生虫特异性迟发型超敏反应（DTH）减弱以及针对三硝基苯（TNP）-利什曼原虫抗原粗可溶性抗原（CSA）的抗TNP IgG1增加，提示Th2型反应过度。抗CD152 Fab片段介导的疾病改善与分泌IFN-γ的细胞数量增加、寄生虫特异性DTH反应增强以及针对TNP-CSA的IgG2a亚型增强有关，提示Th1型反应。与TNP-CSA不同，TNP-钥孔戚血蓝蛋白不会诱导Ig同种型改变，表明抗CD152的免疫调节作用具有抗原特异性。抗CD152抗体诱导的Th亚群早期变化表明，CD152在决定硕大利什曼原虫感染进程中起重要作用，可能是通过改变Th亚群分化来实现的。
