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The Influence of Immunization Route, Tissue Microenvironment, and Cytokine Cell Milieu on HIV-Specific CD8+ T Cells Measured Using Fluidigm Dynamic Arrays.


ABSTRACT: Thirty different genes including cytokines, chemokines, granzymes, perforin and specifically integrins were evaluated in Peyer's patch-KdGag197-205-specific CD8+ T cells (pools of 100 cells) using Fluidigm 48.48 Dynamic arrays following three different prime-boost immunization strategies. Data revealed that the route of prime or the booster immunization differentially influenced the integrin expression profile on gut KdGag197-205-specific CD8+ T cells. Specifically, elevated numbers of integrin ?E and ?D expressing gut KdGag197-205-specific CD8+ T cells were detected following mucosal but not systemic priming. Also, ?E/?7 and ?D/?2 heterodimerization were more noticeable in an intranasal (i.n.)/i.n. vaccination setting compared to i.n./intramuscular (i.m) or i.m./i.m. vaccinations. Moreover, in all vaccine groups tested ?4 appeared to heterodimerize more closely with ?7 then ?1. Also MIP-1?, RANTES, CCR5, perforin and integrin ?4 bio-markers were significantly elevated in i.n./i.m. and i.m./i.m. immunization groups compared to purely mucosal i.n./i.n. delivery. Furthermore, when wild type (WT) BALB/c and IL-13 knockout (KO) mice were immunized using i.n./i.m. strategy, MIP-1?, MIP-1?, RANTES, integrins ?4, ?1 and ?7 mRNA expression levels were found to be significantly different, in mucosal verses systemic KdGag197-205-specific CD8+ T cells. Interestingly, the numbers of gut KdGag197-205-specific CD8+ T cells expressing gut-homing markers ?4?7 and CCR9 protein were also significantly elevated in IL-13 KO compared to WT control. Collectively, our findings further corroborate that the route of vaccine delivery, tissue microenvironment and IL-13 depleted cytokine milieu can significantly alter the antigen-specific CD8+ T cell gene expression profiles and in turn modulate their functional avidities as well as homing capabilities.

SUBMITTER: Trivedi S 

PROVIDER: S-EPMC4422706 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

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