A novel ICOS-independent, but CD28- and SAP-dependent, pathway of T cell-dependent, polysaccharide-specific humoral immunity in response to intact Streptococcus pneumoniae versus pneumococcal conjugate vaccine.
A novel ICOS-independent, but CD28- and SAP-dependent, pathway of T cell-dependent, polysaccharide-specific humoral immunity in response to intact Streptococcus pneumoniae versus pneumococcal conjugate vaccine.
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DOI：
10.4049/jimmunol.181.12.8258
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发表时间：
2008-12-15
期刊：
影响因子：
--
通讯作者：
Snapper CM
中科院分区：
文献类型：
--
作者：
Chen Q;Cannons JL;Paton JC;Akiba H;Schwartzberg PL;Snapper CM
多糖（PS）和蛋白特异性小鼠IgG对完整肺炎链球菌（Pn）的应答都依赖于CD4+ T细胞帮助、b7依赖性共刺激和CD40/CD40配体相互作用。然而，相对于蛋白特异性的IgG应答，初级PS-应答终止得更快，需要更短的T细胞帮助和b7依赖性共刺激，并且不能产生记忆。鉴于ICOS/ICOS-配体相互作用在维持T细胞依赖性Ig反应和促进生发中心反应中的关键作用，我们假设这种相互作用对于ps特异性IgG对Pn的反应不是必需的。我们现在证明，ICOS-/-，相对于WT，小鼠对Pn产生正常的ps特异性IgG同型反应，尽管主要和次要的IgG抗蛋白（即PspA， PspC和PsaA）反应都受到明显抑制。在初级Pn免疫期间注射的阻断性抗icos -配体单抗可抑制初级抗蛋白反应和蛋白质特异性记忆的产生，但在二级免疫期间注射则没有影响。与Pn相反，ICOS-/-小鼠对肺炎球菌结合疫苗的PS-和蛋白特异性IgG反应均被抑制。用完整的Pn或偶联物免疫的ICOS-/-小鼠几乎完全消除了生发中心的形成。最后，尽管缺乏接头分子SAP的小鼠与ICOS-/-小鼠相似（并且可以表现出ICOS表达减少），但我们观察到SAP-/-小鼠对Pn和偶联物的PS-以及蛋白质特异性IgG反应明显缺陷。这些数据定义了一种新的依赖于T细胞、SAP和b7，但不依赖于icos的Ig诱导的滤泡外途径。
Polysaccharide (PS)- and protein-specific murine IgG responses to intact Streptococcus pneumoniae (Pn) are both dependent upon CD4+ T cell help, B7-dependent costimulation, and CD40/CD40-ligand interactions. However, the primary PS-, relative to protein-specific, IgG response terminates more rapidly, requires a shorter period of T cell help and B7-dependent costimulation, and fails to generate memory. In light of the critical role for ICOS/ICOS-ligand interactions in sustaining T cell-dependent Ig responses and promoting germinal center reactions, we hypothesized that this interaction was non-essential for PS-specific IgG responses to Pn. We now demonstrate that ICOS-/-, relative to WT, mice elicit a normal PS-specific IgG isotype response to Pn, despite marked inhibition of both the primary and secondary IgG anti-protein (i.e. PspA, PspC, and PsaA) response. A blocking anti-ICOS-ligand mAb injected during primary Pn immunization inhibits both the primary anti-protein response and the generation of protein-specific memory, but has no effect when injected during secondary immunization. In contrast to Pn, both PS- and protein-specific IgG responses to a pneumococcal conjugate vaccine are inhibited in ICOS-/- mice. ICOS-/- mice immunized with intact Pn or conjugate exhibit nearly complete abrogation in germinal center formation. Finally, although mice that lack the adaptor molecule SAP resemble ICOS-/- mice (and can exhibit decreased ICOS expression), we observe that the PS-, as well as protein-specific IgG responses to both Pn and conjugate are markedly defective in SAP-/- mice. These data define a novel T cell-, SAP-, and B7-dependent, but ICOS-independent, extrafollicular pathway of Ig induction.
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影响因子：
56.9
作者：
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通讯作者：
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64.8
作者：
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影响因子：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1084/jem.176.3.679
发表时间：
1992-09-01
期刊：
The Journal of experimental medicine
影响因子：
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