I’ll make a Tissue Resident Memory (TRM) CD8+ T cell out of you: uncovering the phases of lung TRM development 3087

Abstract Description Tissue-resident memory (TRM) CD8+ T cells in the lungs rapidly respond to influenza reinfection. TRM can express tissue-binding integrins CD49a/CD29 and CD103/B7. When and where TRM develop and acquire their phenotype is debated. To understand the time and location at which TRM precursors are formed, CD8 T cells were isolated from secondary lymphoid organs and lung tissues of uninfected (0 DPI) or influenza-infected (4-10 DPI) mice. CD44+ PA/NP tetramer + (Tet+) cells are first detected in the mediastinal lymph node (LN) and lungs as early as 5 days, half of which were CD49a+, and in the spleen a day later. CD103 was infrequently detected on CD44+Tet+ T cells during the acute phase. In contrast, a sizeable proportion of CD44-Tet- T cells from 0 and 10 DPI were CD103+, suggesting that CD103 expression is not unique to activated T cells or TRM. Next, we addressed whether the activated T cells in the LN were destined to traffic to the lungs. Blocking lymph node egress with FTY720 increased Tet+CD49a+ populations in the LN and reduced them in the lungs. These CD49a+ cells had low expression of circulation and lymph node homing markers, such as CCR7. Lastly, IV-Tet+CD49a+ T cells were detected in other non-infected peripheral tissues during the memory phase, potentially supporting the systemic divergence model. From these experiments, we hypothesize that CD49a expression is induced during activation in the acute phase, and some of these cells may be TRM precursors. Funding Sources NIH/NIA: P01-AI102851 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)