Increased lymph node CD8+ T cell proliferation and memory cell markers upon conditional ablation of Langerhans cells in autoimmune mice (BA14P.215)

Abstract

Abstract Systemic autoimmune diseases such as lupus are characterized by inflammation in many organs. The role of local tissue-resident immune cells in specific organ involvement in these diseases remains unclear. We evaluated the role of Langerhans cells (LC) as prototypic tissue-resident dendritic cells (DC) in eliciting local immune defects in the MRL model of lupus. Injection of diphtheria toxin (DT) in Lang-eGFP.DTR knock-in mice results in depletion of langerin+ dermal DC (dDC) and LC. To assess LC’s role in systemic autoimmunity, we introgressed the knock-in mutation from the stock B6 onto the MRL background. Serial DT injections every 7-10 days exacerbate inflammation in the skin (King et al) and cornea in MRL but not in B6 mice. To investigate underlying mechanisms, we assessed the effect of LC depletion on T cells in skin/eye draining cervical lymph nodes (cLN). There was a significantly higher proliferation of CD8+, but not CD4+, T cells in cLN of LC-ablated than control mice; such effect was not seen in spleen CD8+ T cells. Also, LC-ablated MRL, but not B6 mice, exhibited reduced CD62L on cLN T cells. Further, freshly isolated dDC were more efficient than LC in promoting the proliferation of CD8+, but not CD4+, cNL T cells. Such local regulation of CD8+ T cells may play a role in immune tolerance locally. A defect in this mechanism owing to reduced LC migration in MRL mice (Eriksson and Singh, 2008) may confer skin/eye inflammation, without affecting other organs