Cross- presenting Langerhans cells are required for the early reactivation of resident CD8+ memory T cells in the epidermis

Nadine Kamenjarin, Katrin Hodapp, Felix Melchior, Gregory Harms, Ann-Kathrin Hartmann, Joschka Bartneck, Sabine Muth, Verena K Raker, Christian Becker, Anna Brand, Björn E Clausen, Markus P Radsak, Hansjörg Schild, Hans Christian Probst

Abstract

Tissue-  resident  memory  CD8+  T  cells  (TRM)  reside  at  sites  of  previous  infection,  providing protection against reinfection with the same pathogen. In the skin, TRMpatrol  the  epidermis,  where  keratinocytes  are  the  entry  site  for  many  viral  infec-tions.  Epidermal  TRM  react  rapidly  to  cognate  antigen  encounter  with  the  secre-tion of cytokines and differentiation into cytotoxic effector cells, constituting a first line  of  defense  against  skin  reinfection.  Despite  the  important  protective  role  of  skin TRM, 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 TRM. Our data identify epidermal Langerhans cells that cross- present keratinocyte- derived antigens, as the professional APC indispensable for the early reactivation of TRM in the epidermal layer of the skin