Tissue-Resident T Cells Protect Eyes From Infection

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Despite evidence that effector T cells are recruited to the cornea in response to infections, it is unclear whether memory immune cells are formed to confer long-last­ing immunological protec­tion against reinfection.

In a recent study, re­searchers from the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia, used in vivo microscopy to image T cell responses in the cornea in mice. They found that tissue-resident memory (TRM) T cells were present in the cornea after ocular infection and that corneal TRM cells were activated upon reinfection of the eye.¹ In vivo imaging in humans confirmed the presence of TRM-like immune cells in the cornea.

“We found that T cells come into the eye and stay in the cornea for long periods, constantly patrolling in search of pathogens. These T cells can protect the eye from repeated infections,” said Scott Mueller, PhD, at the University of Melbourne. He added, “Our findings improved our understanding of ocular infections and how to treat them.”

VISUALIZING CORNEAL T CELLS. Representative fluorescence microscopy image of a mouse cornea after HSV infection (T cells = red, corneal nerves = green, and virus-infected cells = yellow).

Approach. The team used two-pho­ton microscopy to visualize immune cells in a mouse model of ocular herpes simplex virus (HSV) infection. They also used in vivo confocal microscopy in healthy people to visualize the im­mune cells in the cornea.

Corneal T cell responses. HSV-spe­cific T cells entered the mouse corneas by day 5 after infection and persisted for at least four weeks—and the cells were dynamic and motile. Using in vivo confocal microscopy, the researchers observed similar motile immune cells in the corneas of healthy volunteers.

“Although the eye is considered an immune-privileged organ, advanced imaging enabled us to visualize corneal immune cells in mice and humans. The discovery that healthy people have mo­tile immune cells in their cornea was surprising and exciting,” Dr. Mueller noted.

Protection against reinfection. Characterization of T cells persisting four weeks after HSV infection demon­strated that these cells expressed mark­ers of TRM cells. The development of TRM cells required the cytokine TGF-β and local antigen recognition. Notably, TRM cells from previously infected mice responded rapidly to in vitro rechal­lenge with HSV, suggesting that these cells may protect against reinfection.

Future steps. “The presence of T cells in the cornea could be used diagnostically. However, we first need to understand the conditions under which corneal T cells are protective and whether T cells can contribute to dis­ease, such as dry eye or corneal trans­plantation rejection,” said Dr. Mueller. The team aims to further characterize the immune cells present in the cornea of healthy people to define their roles in health and disease.

—Christos Evangelou, PhD

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1 Loi JK et al. Cell Rep. 2022;39(8):110852.

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Relevant financial disclosures—Dr. Mueller: None.

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