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TLR4 ligands LPS and MPLA differentially regualte effector and memory CD8 T cell differentiation

ABSTRACT: Here we implemented a simple dendritic cell (DC)-mediated immunization approach to study the effects of commonly used adjuvants, Toll like receptor (TLR) ligands, on effector CD8 T cell differentiation and memory T cell development. To our surprise, we found that the TLR4 ligand LPS was far more superior to other TLR ligands in generating memory CD8 T cells upon immunization. LPS boosted clonal expansion similar to the other adjuvants, but fewer of the activated CD8 T cells died during contraction, generating a larger pool of memory cells. Intriguingly, monophosphoryl lipid A (MPLA), another TLR4 ligand, enhanced clonal expansion of effector CD8 T cells, but also promoted their terminal differentiation and contraction; thus, fewer memory CD8 T cells formed and MPLA-primed animals were less protected against secondary infection compared to those primed with LPS. Furthermore, gene expression profiling revealed that LPS-primed effector cells displayed a stronger pro-memory gene expression signature, whereas the gene expression profile of MPLA-primed effector cells had aligned closer with terminal effector CD8 T cells. Mice that contain small number of P14 CD8 T cells were immunized with DC-33 either alone or in combination with LPS or MPLA. KLRG1loIL-7Rhi MPECs were purified by FACS sort, and mRNA isolated from MPECs was subjected to whole-genome expression profiling using Illumina MouseWG-6 v2.0 Expression BeadChip.

ORGANISM(S): Mus musculus  

SUBMITTER: Hailong Meng   Weiguo Cui  Steven Kleinstein  Susan M Kaech 

PROVIDER: E-GEOD-50764 | ArrayExpress | 2014-06-03



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TLR4 ligands lipopolysaccharide and monophosphoryl lipid a differentially regulate effector and memory CD8+ T Cell differentiation.

Cui Weiguo W   Joshi Nikhil S NS   Liu Ying Y   Meng Hailong H   Kleinstein Steven H SH   Kaech Susan M SM  

Journal of immunology (Baltimore, Md. : 1950) 20140321 9

Vaccines formulated with nonreplicating pathogens require adjuvants to help bolster immunogenicity. The role of adjuvants in Ab production has been well studied, but how they influence memory CD8(+) T cell differentiation remains poorly defined. In this study we implemented dendritic cell-mediated immunization to study the effects of commonly used adjuvants, TLR ligands, on effector and memory CD8(+) T cell differentiation in mice. Intriguingly, we found that the TLR4 ligand LPS was far more sup  ...[more]

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