Parameters Underlying Distinct T Cell-Dependent Polysaccharide-Specific IgG Responses to an Intact Gram-Positive Bacterium versus a Soluble Conjugate Vaccine
Parameters Underlying Distinct T Cell-Dependent Polysaccharide-Specific IgG Responses to an Intact Gram-Positive Bacterium versus a Soluble Conjugate Vaccine
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DOI：
10.4049/jimmunol.0900238
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发表时间：
2009-08-01
影响因子：
4.4
通讯作者：
Snapper, Clifford M.
中科院分区：
文献类型：
--
作者：
Colino, Jesus;Chattopadhyay, Gouri;Snapper, Clifford M.
完整肺炎链球菌 (Pn) 和 PS 结合疫苗的 IgG 抗多糖 (PS) 反应依赖于 CD4(+) T 细胞、B7 依赖性共刺激和 CD40-CD40-配体相互作用。然而，与后者相反，前一种反应是由不依赖 ICOS 的、易于凋亡的滤泡外途径介导的，无法产生 PS 特异性记忆。我们发现，预先存在的 PS 特异性 Igs、细菌表面或颗粒、B 细胞亚群的选择性募集或 Pn 蛋白特异性 CD4(+) T 细胞的激活和募集并不能解释 Put 未能生成 PS 特异性 IgG 记忆的原因。相反，数据表明关键因素可能是完整 Pn 中 PS 与蛋白质缺乏共价连接，这凸显了 PS 荚膜与潜在细菌结构的理化关系对于体内诱导 PS 特异性 Igs 的潜在重要性。免疫学杂志，2009，183：1551-1559。
IgG anti-polysaccharide (PS) responses to both intact Streptococcus pneumoniae (Pn) and PS conjugate vaccines are dependent on CD4(+) T cells, B7-dependent costimulation, and CD40-CD40-ligand interactions. Nevertheless, the former response, in contrast to the latter, is mediated by an ICOS-independent, a poptosis-prone, extrafollicular pathway that fails to generate PS-specific memory. We show that pre-existing PS-specific Igs, the bacterial surface or particulation, selective recruitment of B cell subsets, or activation and recruitment of Pn protein-specific CD4(+) T cells do not account for the failure of Put to generate PS-specific IgG memory. Rather, the data suggest that the critical factor may be the lack of covalent attachment of PS to protein in intact Pn, highlighting the potential importance of the physicochemical relationship of PS capsule with the underlying bacterial structure for in vivo induction of PS-specific Igs. The Journal of Immunology, 2009, 183: 1551-1559.