Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells.
Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells.
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DOI：
10.4049/jimmunol.1600591
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发表时间：
2016-09-01
期刊：
影响因子：
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通讯作者：
Barouch DH
中科院分区：
文献类型：
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作者：
Provine NM;Larocca RA;Aid M;Penaloza-MacMaster P;Badamchi-Zadeh A;Borducchi EN;Yates KB;Abbink P;Kirilova M;Ng'ang'a D;Bramson J;Haining WN;Barouch DH
CD4+ T cell help is critical for optimal CD8+ T cell memory differentiation and maintenance in many experimental systems. Additionally, many reports have identified reduced primary CD8+ T cell responses in the absence of CD4+ T cell help, which often coincides with reduced antigen or pathogen clearance. Here we demonstrate that absence of CD4+ T cells at the time of adenovirus vector immunization of mice led to immediate impairments in early CD8+ T cell functionality and differentiation. Unhelped CD8+ T cells exhibited a reduced effector phenotype, decreased ex vivo cytotoxicity, and decreased capacity to produce cytokines. This dysfunctional state was imprinted within 3 days of immunization. Unhelped CD8+ T cells expressed elevated levels of inhibitory receptors and exhibited transcriptomic exhaustion and anergy profiles by gene set enrichment analysis. Dysfunctional, impaired effector differentiation also occurred following immunization of CD4+ T cell-deficient mice with a poxvirus vector. This study demonstrates that following priming with viral vectors, CD4+ T cell help is required to promote both the expansion and acquisition of effector functions by CD8+ T cells, which is accomplished by preventing immediate dysfunction.
