Soluble antigen and CD40 triggering are sufficient to induce primary and memory cytotoxic T cells
Soluble antigen and CD40 triggering are sufficient to induce primary and memory cytotoxic T cells
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DOI：
10.4049/jimmunol.164.2.725
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发表时间：
2000-01-15
影响因子：
4.4
通讯作者：
Olson, S
中科院分区：
文献类型：
--
作者：
Lefrançois, L;Altman, JD;Olson, S
指导诱导耐受而不是免疫的信号在很大程度上是未知的。CD8 T细胞对可溶性Ag的应答通常导致瞬时共刺激依赖性活化后的缺失耐受。我们证明，CD40信号转导逆转了这种反应的结果，OVA特异性CD8 T细胞的连续转移，随后可溶性OVA免疫导致诱导裂解活性和最佳克隆扩增，只有当CD40通过激动性mAb触发时，CD40信号转导对CD8 T细胞的激活是间接的，因为需要宿主细胞表达CD40。CD40信号传导沿着可溶性Ag免疫也诱导次级淋巴和肠粘膜内源性OVA特异性CD8 T细胞的扩增，如通过MHC四聚体反应性检测的。当包括CD40活化时，从过继转移和内源性CD8 T细胞产生长寿命的次级淋巴和粘膜记忆CD8细胞，粘液和外周CDS记忆细胞表现出组成性Ag特异性裂解活性，粘膜记忆细胞比脾或淋巴结记忆细胞裂解10倍。这些结果表明，在对免疫原性差的可溶性Ag的应答期间，CD40信号传导对于CTL和记忆T细胞诱导是必要和充分的。
The signals directing induction of tolerance rather than immunity are largely unknown. The CD8 T cell response to soluble Ags generally results in deletional tolerance following transient, costimulation-dependent activation. We demonstrated that CD40 signaling reversed the outcome of this response, Adoptive transfer of OVA-specific CD8 T cells followed by soluble OVA immunization resulted in induction of lytic activity and optimal clonal expansion only when CD40 was triggered via an agonistic mAb, Activation of CD8 T cells by CD40 signaling was indirect, because CD40 expression by host cells was required. CD40 signaling along with soluble Ag immunization also induced expansion of secondary lymphoid and intestinal mucosal endogenous OVA-specific CD8 T cells as detected by MHC tetramer reactivity. When CD40 activation was included, long-lived secondary lymphoid and mucosal memory CD8 cells were generated from adoptively transferred and endogenous CD8 T cells, Mucosal and peripheral CDS memory cells exhibited constitutive Ag-specific lytic activity, with mucosal memory cells being 10-fold more lytic than splenic or lymph node memory cells. These results demonstrated that CD40 signaling during a response to a poorly immunogenic soluble Ag aas necessary and sufficient for CTL and memory T cell induction.