Muthukkumar S, Goldstein J, Stein K E
Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
J Immunol. 2000 Nov 1;165(9):4803-13. doi: 10.4049/jimmunol.165.9.4803.
The immune response to polysaccharide (PS) Ags in mice is delayed during ontogeny even when administered in a thymus-dependent (TD) form. In this study, Neisseria meningitidis group C PS-tetanus toxoid conjugate (MCPS-TT) vaccine was used to examine whether the delay in the development of Ab responses to TD PS conjugate vaccines in neonatal mice is due to defective Ag presentation. The results show that B cells and dendritic cells (DC) from 3- and 7-day-old mice were severely defective in presenting TT and MCPS-TT to Ag-specific T cell clones. The ability of these cells to present Ag reaches adult levels by 4 wk. The development of anti-MCPS and anti-TT Abs in neonatal mice parallels the functional ability of their APC to present Ag. DC from neonatal mice expressed very low levels of MHC class II, costimulatory molecules B7.1, B7.2, and CD11c but high levels of monocyte-specific markers F4/80 and CD11b and granulocyte marker, Ly6G. Significant changes in the expression of these markers were observed as the age of the mice increased. MHC class II, B7.1 and B7.2, and CD11c all increased with age, reaching adult levels between 3 and 4 wk, concurrent with the function of APC. These results demonstrate that one reason neonates fail to produce high titers of anti-PS Abs even when immunized in a TD form is that their B cells and DC are not fully functional.
在个体发育过程中,小鼠对多糖(PS)抗原的免疫反应会延迟,即使以胸腺依赖性(TD)形式给药也是如此。在本研究中,使用脑膜炎奈瑟菌C群PS-破伤风类毒素结合物(MCPS-TT)疫苗来检验新生小鼠对TD PS结合疫苗的抗体反应发育延迟是否是由于抗原呈递缺陷所致。结果显示,3日龄和7日龄小鼠的B细胞和树突状细胞(DC)在将TT和MCPS-TT呈递给抗原特异性T细胞克隆方面存在严重缺陷。这些细胞呈递抗原的能力在4周时达到成年水平。新生小鼠中抗MCPS和抗TT抗体的发育与其抗原呈递细胞呈递抗原的功能能力平行。新生小鼠的DC表达非常低水平的MHC II类分子、共刺激分子B7.1、B7.2和CD11c,但表达高水平的单核细胞特异性标志物F4/80和CD11b以及粒细胞标志物Ly6G。随着小鼠年龄的增加,观察到这些标志物的表达有显著变化。MHC II类分子、B7.1和B7.2以及CD11c均随年龄增加,在3至4周时达到成年水平,与抗原呈递细胞的功能同步。这些结果表明,即使以TD形式免疫,新生儿也无法产生高滴度抗PS抗体的一个原因是其B细胞和DC功能不全。