Taborda C P, Casadevall A
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
J Immunol. 2001 Feb 1;166(3):2100-7. doi: 10.4049/jimmunol.166.3.2100.
The IgM mAbs 12A1 and 13F1 are protective and nonprotective, respectively, against lethal Cryptococcus neoformans infection in mice. To better understand the variables that contribute to IgM efficacy against C. neoformans, we studied the effects of inoculum size, route of infection, and Ab dose for each of these mAbs. mAb 13F1 did not prolong survival under any condition studied. mAb 12A1 prolonged survival after the administration of certain Ab doses after i.p. infection with defined inocula and promoted phagocytosis, agglutination, and the formation of inflammatory cell rings around yeast cells in vivo. Large Ab doses of mAb 12A1 resulted in either no protection or enhanced infection, consistent with a prozone-like effect. Investigation of this phenomenon revealed that the fungal cell was protected against microbicidal nitrogen-derived oxidants when large amounts of Ab were bound to the C. neoformans capsule. mAb 12A1 was opsonic in vitro for peritoneal, but not splenic or alveolar macrophages. In summary, our results indicate that IgM efficacy against C. neoformans is a function of the route of infection, inoculum, and Ab dose and is associated with its ability to promote opsonization, agglutination, and phagocytic ring formation in vivo. The occurrence of the prozone-like phenomenon implies that high Ab titers are not necessarily beneficial in assuring protection against certain pathogens and that caution should be exercised in using high Ab titer as a measure for vaccine efficacy.
IgM单克隆抗体12A1和13F1分别对小鼠致死性新型隐球菌感染具有保护作用和无保护作用。为了更好地理解影响IgM抗新型隐球菌效力的变量，我们研究了接种量、感染途径和每种单克隆抗体的抗体剂量的影响。在任何研究条件下，单克隆抗体13F1都不能延长生存期。腹腔注射确定接种量后，给予一定剂量的单克隆抗体12A1可延长生存期，并在体内促进吞噬作用、凝集作用以及酵母细胞周围炎症细胞环的形成。大剂量的单克隆抗体12A1要么没有保护作用，要么增强感染，这与前带样效应一致。对这一现象的研究表明，当大量抗体与新型隐球菌荚膜结合时，真菌细胞可免受杀菌性氮源氧化剂的作用。单克隆抗体12A1在体外对腹腔巨噬细胞具有调理作用，但对脾巨噬细胞或肺泡巨噬细胞则没有。总之，我们的结果表明，IgM抗新型隐球菌的效力是感染途径、接种量和抗体剂量的函数，并且与其在体内促进调理作用、凝集作用和吞噬环形成的能力有关。前带样现象的出现意味着高抗体滴度不一定有利于确保对某些病原体的保护，并且在将高抗体滴度用作疫苗效力的衡量标准时应谨慎行事。
