Circulation of gut-preactivated naïve CD8 <sup>+</sup> T cells enhances antitumor immunity in B cell-defective mice
Maryam Akrami, Rosemary J. Menzies, Kenji Chamoto, Michio Miyajima, Ryuji Suzuki, Hiroyuki Sato, Akiko Nishii, Michio Tomura, Sidonia Fagarasan, Tasuku Honjo
Abstract
Significance Accumulating evidence supports important roles for the microbiota in health and disease. The absence of IgA induces microbial dysbiosis, leading to inflammation in the gut environment. Here, we found that the strong antitumor immunity of B cell-deficient mice is due to their microbial dysbiosis, leading to activation of type I interferon (IFN) signaling in peripheral CD8 + T cells. The constant circulation of CD8 + T cells, particularly the naïve subset between the periphery and the gut, leads to the induction of a gut-educated naïve subpopulation in the periphery. Exposure to type I IFN in the gut endows this naïve subpopulation with superior effector potential. These data provide important insights into how the gut environment can shape peripheral immunity.