Saoudi A, Kuhn J, Huygen K, de Kozak Y, Velu T, Goldman M, Druet P, Bellon B
INSERM U28, Hôpital Broussais, Paris, France.
Eur J Immunol. 1993 Dec;23(12):3096-103. doi: 10.1002/eji.1830231208.
Mercuric chloride (HgCl2) injections protect (Lewis x Brown-Norway) F1 (F1) rats against experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal S antigen (S-Ag); in contrast HgCl2-injected F1 rats develop EAU following transfer of lymph node (LN) cells from rats immunized with S-Ag alone. In the present study we demonstrate that the ability of LN cells from rats protected against EAU to transfer the disease into naive F1 rats was considerably reduced. These LN cells neither produced interleukin (IL)-2 nor (interferon (IFN)-gamma but exhibited mRNA for IL-4. In contrast, LN cells from diseased rats easily transferred EAU into naive F1 rats, produced significant IL-2 and IFN-gamma levels but barely exhibited mRNA for IL-4. Furthermore protected rats predominantly produced IgG1 anti-S-Ag antibodies, while diseased rats produced IgG2b anti-S-Ag antibodies and the increase in expression of MHC class II molecules on B cells was higher in protected rats than in diseased rats. These data suggest that (1) to exert a protective effect, HgCl2 must act at an early stage of differentiation of precursors of S-Ag specific T cells, and (2) this effect is related to the preferential activation of TH2 cells to the detriment of uveitogenic TH1 cells. Finally, these results indicate that activation of TH2 cells protect from a TH1-dependent autoimmune disease.
注射氯化汞(HgCl2)可保护(Lewis×Brown-Norway)F1大鼠免受因用视网膜S抗原(S-Ag)免疫诱导的实验性自身免疫性葡萄膜视网膜炎(EAU);相反,注射HgCl2的F1大鼠在单独用S-Ag免疫的大鼠的淋巴结(LN)细胞转移后会发生EAU。在本研究中,我们证明,受保护免受EAU的大鼠的LN细胞将疾病转移到未免疫的F1大鼠中的能力大大降低。这些LN细胞既不产生白细胞介素(IL)-2,也不产生干扰素(IFN)-γ,但表现出IL-4的mRNA。相反,患病大鼠的LN细胞很容易将EAU转移到未免疫的F1大鼠中,产生显著水平的IL-2和IFN-γ,但几乎不表现出IL-4的mRNA。此外,受保护的大鼠主要产生IgG1抗S-Ag抗体,而患病大鼠产生IgG2b抗S-Ag抗体,并且受保护大鼠中B细胞上MHC II类分子表达的增加高于患病大鼠。这些数据表明:(1)为发挥保护作用,HgCl2必须在S-Ag特异性T细胞前体分化的早期起作用;(2)这种作用与TH2细胞的优先激活有关,从而损害致葡萄膜炎的TH1细胞。最后,这些结果表明TH2细胞的激活可预防TH1依赖性自身免疫性疾病。