The cornea has traditionally been described as an immune‑privileged tissue. Recent observations, however, report the presence of T cells within clinically non‑inflamed human cornea, challenging a strictly immune‑excluded view. The study summarized here used multiple complementary approaches in human donor tissue and murine models to define the identity of corneal T cells, to test whether systemic immune events influence their presence, and to explore factors associated with their abundance.
Immunofluorescence staining and confocal imaging of clinically non‑inflamed human donor corneas demonstrated the presence of CD3+ T cells within the corneal epithelium. Subsequent flow cytometric analysis of corneal tissue indicated that these T cells were predominantly CD8+ and displayed a tissue‑resident memory T (TRM) cell phenotype. These multimodal human data establish that bona fide TRM‑like T cells are present in healthy human cornea rather than appearing only after overt inflammation.
In vivo confocal microscopy performed as part of the study revealed that corneal T cell abundance increased with chronological age. The increase in abundance was particularly noted in males compared with females, suggesting that accumulation of corneal T cells is shaped by both age and biological sex. The authors interpret these associations as consistent with accumulation driven by cumulative systemic immune experience over time.
Young specific pathogen‑free (SPF) mice lacked detectable corneal T cells in the experiments described. In contrast, when mice were subjected to systemic infection with pathogens that do not normally target the cornea, the animals developed long‑lived, TRM‑like CD8+ T cells in the cornea. This experimental observation supports the conclusion that systemic immune activation can promote establishment of corneal TRM even in the absence of direct corneal infection. The murine data thus provide a tractable model to investigate how systemic immune events seed or shape corneal immune surveillance.
Together, the human and mouse data indicate that the healthy human cornea is not devoid of adaptive immune cells: it harbors CD8+ TRM‑phenotype T cells localized within the epithelium. The increase in corneal T cell numbers with age, and the greater accumulation in males, suggest that lifetime systemic immune exposures contribute to building a corneal TRM compartment. The murine infection model further implies that peripheral immune activation, even by pathogens that are not corneotropic, can induce durable corneal TRM. These findings are relevant to understanding baseline corneal immunity, potential sex‑ and age‑related differences in corneal immune responses, and how systemic infections or vaccinations might influence ocular immune status.
Because the available source text was limited to the abstract fragment, readers should consult the full preprint and supplementary materials for complete methods, datasets, and the authors' detailed conclusions. The preprint DOI and supplementary material were provided by the authors for those seeking the complete dataset.
The reported data support that the human cornea harbors resident CD8+ TRM cells and that their presence and accumulation are influenced by systemic immune experience, age, and biological sex. Murine infection models corroborate a role for systemic immune activation in establishing corneal TRM. Full mechanistic insight and quantitative findings were not included in the available abstract excerpt; the full preprint should be reviewed for complete results and interpretation.