Introduction/Rationale: Recent evidence shows the dominance of memory T cells in the immune landscape of the mouse lacrimal gland (LG) but their role in idiopathic lacrimal dysfunction is unknown, and there is no current model able to selectively manipulate this subset of cells. We hypothesized that viral infection results in resident memory T cell (TRM) establishment in the LG, and that reactivation of TRM results in pro-inflammatory cytokine production and reduction in lacrimal secretions.
Methods: Female mice received an adoptive transfer of OT-I T cells followed by intranasal (IN) infection of vesicular stomatitis virus expressing OVA. A minimum of 30 days later, LGs were harvested for immunohistochemistry (IHC) or processed for flow cytometry. For IHC, LGs were stained for OT-Is, and for flow cytometry, LG lymphocytes were stained for TRM markers. Lacrimation was assessed using in vitro measurement of protein release from LGs in response to neural stimuli.
Results: Data showed that VSVova infection seeds persistent antigen-experienced CD8+ T cells and TRM populations in the murine LG. Following infection, a subset of LG CD8s were CD69+CD103- and smaller subset were CD69+CD103+. Also, a subset of CD8s were OT-Is, found by IHC and flow cytometry. Following in vitro reactivation, OT-Is expressed high levels of cytokines.
Conclusion: These data indicate that VSVova results in LG TRM populations, and that LG OT-Is can reactivate in vitro. Ongoing work is testing the impact of TRM reactivation on LG inflammation and function.
