CD8+ T Cell Activation Leads to Constitutive Formation of Liver Tissue-Resident Memory T Cells that Seed a Large and Flexible Niche in the Liver

• DOI: 10.1016/j.celrep.2018.08.094
• Publication Date: 2018-10-02T14:41:36Z
• Authors: Lauren E. Holz; Julia E. Prier; David Freestone; Thiago M. Steiner; Kieran English; Darryl N. Johnson; Vanessa Mollard; Anton Cozijnsen; Gayle M. Davey; Dale I. Godfrey; Katsuyuki Yui; Laura K. Mackay; Mireille H. Lahoud; Irina Caminschi; Geoffrey I. McFadden; Patrick Bertolino; Daniel Fernandez-...; William R. Heath
• Keywords: Male; QH301-705.5; 1.1 Normal biological development and functioning; malaria; tissue-resident memory; 610; T cell memory; CD8-Positive T-Lymphocytes; Inbred C57BL; Lymphocyte Activation; Hepatitis; Vaccine Related; Epitopes; Mice; 03 medical and health sciences; 0302 clinical medicine; 616; 2.1 Biological and endogenous factors; Animals; anzsrc-for: 31 Biological Sciences; Biology (General); Interleukin-15; Liver Disease; Inflammatory and immune system; 3 Good Health and Well Being; Adoptive Transfer; 3. Good health; Mice, Inbred C57BL; niche; Infectious Diseases; Liver; Immunization; liver immunology; Digestive Diseases; Immunologic Memory; 31 Biological Sciences

Liver tissue-resident memory T (Trm) cells migrate throughout the sinusoids and are capable of protecting against malaria sporozoite challenge. To gain an understanding of liver Trm cell development, we examined various conditions for their formation. Although liver Trm cells were found in naive mice, their presence was dictated by antigen specificity and required IL-15. Liver Trm cells also formed after adoptive transfer of in vitro-activated but not naive CD8+ T cells, indicating that activation was essential but that antigen presentation within the liver was not obligatory. These Trm cells patrolled the liver sinusoids with a half-life of 36 days and occupied a large niche that could be added to sequentially without effect on subsequent Trm cell cohorts. Together, our findings indicate that liver Trm cells form as a normal consequence of CD8+ T cell activation during essentially any infection but that inflammatory and antigenic signals preferentially tailor their development.