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Dendritic cells (DCs) are composed of multiple subsets that play a dual role in inducing immunity and tolerance. However, it is unclear how CD205+ conventional DCs (cDCs) control immune responses in vivo. Here we generated knock-in mice with the selective conditional ablation of CD205+ cDCs. CD205+ cDCs contributed to antigen-specific priming of CD4+ T cells under steady-state conditions, whereas they were dispensable for antigen-specific CD4+ T-cell responses under inflammatory conditions. In contrast, CD205+ cDCs were required for antigen-specific priming of CD8+ T cells to generate cytotoxic T lymphocytes (CTLs) mediated through cross-presentation. Although CD205+ cDCs were involved in the thymic generation of CD4+ regulatory T cells (Tregs), they maintained the homeostasis of CD4+ Tregs and CD4+ effector T cells in peripheral and mucosal tissues. On the other hand, CD205+ cDCs were involved in the inflammation triggered by Toll-like receptor ligand as well as bacterial and viral infections. Upon microbial infections, CD205+ cDCs contributed to the cross-priming of CD8+ T cells for generating antimicrobial CTLs to efficiently eliminate pathogens, whereas they suppressed antimicrobial CD4+ T-cell responses. Thus, these findings reveal a critical role for CD205+ cDCs in the regulation of T-cell immunity and homeostasis in vivo. [ABSTRACT FROM AUTHOR]

CD26 is a 110 kDa surface glycoprotein with intrinsic dipeptidyl peptidase IV activity that is expressed on numerous cell types and has a multitude of biological functions. The role of CD26 in immune regulation has been extensively characterized, with recent findings elucidating its linkage with signaling pathways and structures involved in T-lymphocyte activation as well as antigen presenting cell-T-cell interaction. In this paper, we will review emerging data on CD26-mediated immune regulation suggesting that CD26 may be an appropriate therapeutic target for the treatment of selected immune disorders as well as Middle East respiratory syndrome coronavirus. Moreover, we have had a long-standing interest in the role of CD26 in cancer biology and its suitability as a novel therapeutic target in selected neoplasms. We reported robust in vivo data on the anti-tumor activity of anti-CD26 monoclonal antibody in mouse xenograft models. We herein review significant novel findings and the early clinical development of a CD26-targeted therapy in selected immune disorders and cancers, advances that can lead to a more hopeful future for patients with these intractable diseases.