SCIENCE@home

ABSTRACT

Group 1 innate lymphoid cells (ILCs), which comprise both natural killer (NK) cells and ILC1s, are important innate effectors that can also positively and negatively influence adaptive immune responses. The latter function is generally ascribed to the ability of NK cells to recognize and kill activated T cells. Here, we used multiphoton intravital microscopy in mouse models of hepatitis B to study the intrahepatic behavior of group 1 ILCs and their cross-talk with hepatitis B virus (HBV)–specific CD8+ T cells. We found that hepatocellular antigen recognition by effector CD8+ T cells triggered a prominent increase in the number of hepatic NK cells and ILC1s. Group 1 ILCs colocalized and engaged in prolonged interactions with effector CD8+ T cells undergoing hepatocellular antigen recognition; however, they did not induce T cell apoptosis. Rather, group 1 ILCs constrained CD8+ T cell proliferation by controlling local interleukin-2 (IL-2) availability. Accordingly, group 1 ILC depletion, or genetic removal of their IL-2 receptor a chain, considerably increased the number of intrahepatic HBV-specific effector CD8+ T cells and the attendant immunopathology. Together, these results reveal a role for group 1 ILCs in controlling T cell–mediated liver immunopathology by limiting local IL-2 concentration and have implications for the treatment of chronic HBV infection. Description Competition for IL-2 between group 1 ILCs and CD8+ T cells limits liver immunopathology. Friendly competition in the liver Hepatotropic viruses such as hepatitis B virus (HBV) can cause chronic liver disease in part by generating antiviral effector T cells that subsequently contribute to collateral tissue damage. Using intravital microscopy in mouse models of HBV infection, Fumagalli et al. demonstrate that group 1 innate lymphoid cells (ILCs), comprising natural killer cells and ILC1s, interact closely with HBV-specific CD8+ T cells in the liver and protect against liver damage caused by effector T cells. Rather than directly killing nearby CD8+ T cells, group 1 ILCs limited effector T cell responses by competing for local IL-2 required for their proliferation. These results provide insight into cross-talk between liver lymphocyte populations and identify a regulatory function for group 1 ILCs in constraining antiviral T cell responses.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-72 of 72 references · Page 1 of 1

CITED BY

Showing 1-29 of 29 citing papers · Page 1 of 1