In Lm-OVA infected mice that initially received equal numbers of OT-I Rgs1+/+ and OT-I Rgs1-/- cells, the antigen-specific, Rgs1-deficient CD8+ TRM cells were underrepresented in the small intestinal mucosa from day 6 post-infection (p.i.)until the end of the observation period, i.e., on day 30 p.i. Finally, by utilizing a heterologous in vivo re-challenge model, we show that genetic deletion of Rgs1 in antigen-specific CD8+ TRM cells resulted in significantly impaired intestinal barrier immunity, accompanied by increased systemic pathogen dissemination. The gene discussed is CD8A; the disease is infection.