Oral Presentation The Australasian Society for Immunology 2017 Annual Scientific Meeting

Protein tyrosine phosphatase non-receptor type 2 regulates development and function of skin-resident memory CD8 T cells (#58)

Katharina Hochheiser 1 , Florian Wiede 2 , Moshe Olshansky 3 , Brendan Russ 3 , Stephen Turner 3 , Tony Tiganis 2 , Sammy Bedoui 1 , Thomas Gebhardt 1
  1. Department of Microbiology and Immunology, University of Melbourne, Melbourne, VIC, Australia
  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia
  3. Department of Microbiology, Monash University, Clayton, VIC, Australia

T cells play a central role in immune protection against pathogens. After resolution of an infection, tissue-resident memory T cells (TRM) provide a high degree of protection against localised infection. However, they may also drive aberrant immune responses associated with autoimmunity. Here, we investigated the role of the protein tyrosine phosphatase non-receptor type 2 (Ptpn2) in TRM formation and function using models of Herpes simplex virus skin infection and skin autoimmunity. We observed a profound defect of Ptpn2-deficient CD8 T cells in forming TRM populations in vivo. Mechanistically, Ptpn2-deficient CD8 T cells displayed a defect in seeding the skin with KLRG1- TRM precursors. Normalising memory precursor frequencies by cell sorting or modulation of T cell activation conditions rescued the defect in TRM generation. Finally, Ptpn2-deficient TRM cells in skin accelerated disease onset and severity in an inducible mouse model of autoimmune dermatitis compared to Ptpn2-competent T cells. Our study reveals a dual role for Ptpn2 in skin TRM, promoting TRM development by enhancing precursor frequencies and regulating potentially detrimental effector functions in the context of skin autoimmunity.