Abstract
Abstract Vaccines that provide long-term protection against a pathogenic infection often use adjuvants to boost the immune response to less immunogenic antigens. Lipopolysaccharide (LPS) is such an adjuvant that enhances CD4 T cell clonal expansion, survival and IFN-γ production. Similarly, engagement of OX40 receptor (CD134) on antigen activated CD4 T cells increases CD4 T cell activation and clonal expansion. Administration of LPS and CD134 costimulation together profoundly increases the Ag-specific CD4 T clonal expansion, survival and memory. It is known that LPS induced TRIF signaling is needed CD4 and CD8 T migration to liver, lung and spleen as well as for IFNγ production. TRIF downstream activates Type I interferon which can upregulate co-stimulatory molecules on APC and mediate CD4 T cell priming and expansion. Hence our goal is to study how LPS induced Type I Interferon together with CD134 costimulation impacts antigen specific CD4 T cell expansion, migration and effector potential in lymphoid and non-lymphoid organs. Our results show that, IFNAR blockade reduced antigen-specific CD4 T cell expansion and migration to liver on days 6 and 12 on immunization with LPS and CD134 agonist. In pLN however, IFNAR blockade reduced T cell expansion and migration on day 6, but by day 12 T cells began to accumulate. Additionally even though Type I interferon signaling was needed for IFNγ secretion by Th1 cells in pLN, it actually reduced IFNγ and TNFα secretion of Th1 cells in liver.
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