Abstract
Non-recirculating resident memory (TRM) and recirculating T cells mount vigorous immune responses to both self and foreign antigens in barrier tissues like the skin, lung and gastrointestinal tract. Using impression cytology followed by flow cytometry we identified two TRM subsets and four recirculating T-subsets in the healthy human ocular surface. In dry eye disease, principal component analysis (PCA) revealed two clusters of patients with distinct T-cell signatures. Increased conjunctival central memory and naïve T cells characterized Cluster-1 patients, and increased CD8+ TRMs and CD4+ recirculating memory T cells characterized Cluster-2 patients. Interestingly these T-cell signatures are associated with different clinical features: the first signature correlated with increased ocular redness, and the second with reduced tear break up times. These findings open the door to immune-based characterization of dry eye disease and T-subset specific immunotherapies to suppress T-subsets involved in disease. They may also help with patient stratification during clinical trials of immunomodulators.
Highlights
Non-recirculating resident memory (TRM) and recirculating T cells mount vigorous immune responses to both self and foreign antigens in barrier tissues like the skin, lung and gastrointestinal tract
Infections or antigenic challenge cause naïve T cells to differentiate into distinct memory T cell populations that are distinguished by their expression of the chemokine receptor CCR7 and the tyrosine phosphatase CD45 (TCM: central memory T cells; TEM: effector memory T cells: TEMRA: effector memory T cells that have reacquired expression of CD45RA and lost CD45RO) (Fig. 1A)[1]
We selected 39 healthy controls based on the absence of history of dry eye disease (DED) symptoms in the preceding 3 weeks determined by the SPEED (Standard Patient Evaluation of Eye Dryness) questionnaire, and normal scores on the Schirmer’s Test and non-invasive tear breakup time (NI-TBUT) (Supplementary Table S1, Supplementary Figure S1)
Summary
Non-recirculating resident memory (TRM) and recirculating T cells mount vigorous immune responses to both self and foreign antigens in barrier tissues like the skin, lung and gastrointestinal tract. Increased conjunctival central memory and naïve T cells characterized Cluster-1 patients, and increased CD8+ TRMs and CD4+ recirculating memory T cells characterized Cluster-2 patients These T-cell signatures are associated with different clinical features: the first signature correlated with increased ocular redness, and the second with reduced tear break up times. These findings open the door to immune-based characterization of dry eye disease and T-subset specific immunotherapies to suppress T-subsets involved in disease. While T cell subsets have been described in the conjunctiva[13], the relative proportions of TRM and recirculating T cells at this barrier surface have not been studied in humans or animal models Such information could provide insights into ocular surface inflammation. It develops due to stress, autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome), chemical injury, blepharitis, infections, meibomian gland dysfunction and allergies, and more devastating conditions such as Steven Johnson syndrome and graft-versus-host disease[15,16,17,18,19,20,21,22]
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