Induction of a Th1 Response from Th2 Polarized T Cells by Activated Dendritic Cells: Dependence on TCR:pMHC Interaction, ICAM-1, IL-12 (92.7)

Abstract

Abstract Dendritic cells (DC) are important regulators of T cell immunity. The degree of stimulation, the pattern of co-stimulatory molecules expressed, and the cytokines secreted by DC dictate the nature of the effector and memory cells generated, particularly with respect to their Th1 or Th2 phenotypes. In this report we demonstrate that addition of activated DC to spleen cultures containing established Th2 polarized CD4+ T cells was sufficient to suppress Th2 and to induce Th1 cytokines in a recall response, a phenomenon referred to as phenotype reversal. The ability of activated DC to induce phenotype reversal displayed exquisite antigen specificity. The DC activator B7-DC XAb was more than 10,000-fold more efficient at inducing phenotype reversal than the TLR agonists, CpG-ODN and Gardiquimod. Characterization of the mechanisms governing phenotype reversal revealed the requirement for cognate interaction between the TCR: pMHC complex, the expression of the co-stimulation/adhesion molecule ICAM-1, and secretion of IL-12 and IFNƒ×ƒnby the activated DC. Requirement for the co-stimulation/adhesion molecule SLAM was found to be quantitative. Thus, activation of DC, particularly by cross linking B7-DC, can modulate well established Th2 T cell responses in an antigen specific manner.