Cross-presenting Langerhans cells are required for the early reactivation of resident CD8 <sup>+</sup> memory T cells in the epidermis
Nadine Kamenjarin, Katrin Hodapp, Felix Melchior, Gregory S. Harms, Ann‐Kathrin Hartmann, Joschka Bartneck, Sabine Muth, Verena Raker, Christian Becker, Anna Brand, Björn E. Clausen, Markus P. Radsak, Hansjörg Schild, Hans Christian Probst
Abstract
Tissue-resident memory CD8 + T cells (T RM ) reside at sites of previous infection, providing protection against reinfection with the same pathogen. In the skin, T RM patrol the epidermis, where keratinocytes are the entry site for many viral infections. Epidermal T RM react rapidly to cognate antigen encounter with the secretion of cytokines and differentiation into cytotoxic effector cells, constituting a first line of defense against skin reinfection. Despite the important protective role of skin T RM , it has remained unclear, whether their reactivation requires a professional antigen-presenting cell (APC). We show here, using a model system that allows antigen targeting selectively to keratinocytes in a defined area of the skin, that limited antigen expression by keratinocytes results in rapid, antigen-specific reactivation of skin T RM . Our data identify epidermal Langerhans cells that cross-present keratinocyte-derived antigens, as the professional APC indispensable for the early reactivation of T RM in the epidermal layer of the skin.