IL-6 Production by TLR-Activated APC Broadly Enhances Aged Cognate CD4 Helper and B Cell Antibody Responses In Vivo.
Vinayak BrahmakshatriyaYi KuangPriyadharshini DevarajanJingya XiaWenliang ZhangAllen Minh VongSusan L SwainPublished in: Journal of immunology (Baltimore, Md. : 1950) (2017)
Naive CD4 T cell responses, especially their ability to help B cell responses, become compromised with aging. We find that using APC pretreated ex vivo with TLR agonists, polyinosinic-polycytidylic acid and CpG, to prime naive CD4 T cells in vivo, restores their ability to expand and become germinal center T follicular helpers and enhances B cell IgG Ab production. Enhanced helper responses are dependent on IL-6 production by the activated APC. Aged naive CD4 T cells respond suboptimally to IL-6 compared with young cells, such that higher doses are required to induce comparable signaling. Preactivating APC overcomes this deficiency. Responses of young CD4 T cells are also enhanced by preactivating APC with similar effects but with only partial IL-6 dependency. Strikingly, introducing just the activated APC into aged mice significantly enhances otherwise compromised Ab production to inactivated influenza vaccine. These findings reveal a central role for the production of IL-6 by APC during initial cognate interactions in the generation of effective CD4 T cell help, which becomes greater with age. Without APC activation, aging CD4 T cell responses shift toward IL-6-independent Th1 and CD4 cytotoxic Th cell responses. Thus, strategies that specifically activate and provide Ag to APC could potentially enhance Ab-mediated protection in vaccine responses.
Keyphrases
- immune response
- toll like receptor
- signaling pathway
- gene expression
- type diabetes
- dendritic cells
- hiv infected
- dna methylation
- metabolic syndrome
- induced apoptosis
- inflammatory response
- oxidative stress
- genome wide
- adipose tissue
- quantum dots
- skeletal muscle
- endoplasmic reticulum stress
- bone marrow
- cell death
- smoking cessation
- cell cycle arrest
- anti inflammatory
- nuclear factor
- replacement therapy