Inhibition of functional T cell priming and contact hypersensitivity responses by treatment with anti-secondary lymphoid chemokine antibody during hapten sensitization

Recent studies have suggested a pivotal role for secondary lymphoid chemoki ne (SLC) in directing dendritic cell trafficking from peripheral to lymphoi d tissues. As an extension of these studies, we examined the consequences o f anti-SLC Ab treatment during Ag priming on T cell function in an inflamma tory response, We used a model of T cell-mediated inflammation, contact hyp ersensitivity (CHS), where priming of the effector T cells is dependent upo n epidermal dendritic cell, Langerhans cells, and migration from the hapten sensitization site in the skin to draining lymph nodes. A single injection of anti-SLC Ab given at the time of sensitization with FITC inhibited Lang erhans cell migration into draining lymph nodes for at least 3 days, The CH S response to hapten challenge was inhibited by anti-SLC Ab treatment in a dose-dependent manner. Despite the inhibition of CHS, T cells producing IFN -gamma following in vitro stimulation with anti-CDS mAb or with hapten-labe led cells were present in the skin-draining lymph nodes of mice treated wit h anti-SLC Ab during hapten sensitization, These T cells were unable, howev er, to passively transfer CHS to naive recipients. Animals treated with ant i-SLC Ab during hapten sensitization were not tolerant to subsequent sensit ization and challenge with the hapten, In addition, anti-SLC Ab did not inh ibit CHS responses when given at the time of hapten challenge. These result s indicate an important role for SLC during sensitization for CHS and sugge st a strategy to circumvent functional T cell priming for inflammatory resp onses through administration of an Ab inhibiting dendritic cell trafficking .