title: Temporary CXCR3 and CCR5 antagonism following vaccination enhances memory CD8 T cell immune responses.
abstract: Although current vaccination strategies have been successful at preventing a variety of human diseases, attempts at vaccinating against some pathogens such as AIDS and tuberculosis (TB) have been more problematic, largely in that abnormally high numbers of antigen specific CD8+ T cells are required for protection. This study assessed the effect of temporarily dampening the chemokine receptor CXCR3 and CCR5 after vaccination on host immune responses by the administration of TAK-779, a small molecule CXCR3 and CCR5 antagonists commonly used to inhibit HIV infection. Our results showed that the use of TAK-779 enhanced memory CD8+ T cell immune responses both qualitatively and quantitatively. Treatment with TAK-779 following vaccination of an influenza virus antigen resulted in enhanced memory generation with more CD8+CD127+ memory precursor and fewer terminally differentiated effector CD8+CD69+ T cells. These memory T cells were able to become IFN-γ-secreting effector cells when re-encountered the same antigen, which can further enhance the efficacy of vaccination. The mice vaccinated in the presence of TAK-779 were better protected upon influenza virus challenge than the control. These results showed that vaccination while temporarily inhibiting chemokine receptor CXCR3 and CCR5 by TAK-779 could be a promising strategy to generate large number of protective memory CD8+ T cells.
authors.affiliation: Department of microbiology and microbial engineering, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of microbiology and microbial engineering, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of microbiology and microbial engineering, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Tian
authors.affiliation: Department of microbiology and microbial engineering, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
authors.forename: Zihan
authors.initials: Z
authors.lastname: Ran
authors.affiliation: Department of microbiology and microbial engineering, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Biosynthesis, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of microbiology and microbial engineering, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
authors.forename: Fangting
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of microbiology and microbial engineering, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of microbiology and microbial engineering, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhong
keywords: CCR5; CD8 memory; CXCR3; Vaccination; chemokines