Cytokine Production and Antigen Recognition by Human Mucosal Homing Conjunctival Effector Memory CD8+ T Cells

Williams, Gwyn Samuel; Pachnio, Annette; Long, Hao; Rauz, Saaeha; Curnow, S. John

doi:10.1167/iovs.14-15133

Cited by 7 publications

(9 citation statements)

References 38 publications

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“…Using immunohistochemistry on conjunctival biopsies, the involvement of CD4 + and CD8 + T cells in Sjogren and non-Sjogren DED patients has been reported3839. More recently, impression cytology has been used to demonstrate the preponderance of mucosal-homing CD8 + T EM cells in the conjunctiva of healthy individuals40.…”

Section: Discussionmentioning

confidence: 99%

“…Although these are relatively non-invasive, they may show a predisposition towards more superficial intraepithelial T cells as opposed to stromal cells and follicular T cells, and therefore do not represent the entire T cell population in the ocular surface mucosa. However, impression cytology is a standard procedure used in various studies of ocular surface disease1340.…”

Section: Discussionmentioning

confidence: 99%

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Tissue resident memory T cells in the human conjunctiva and immune signatures in human dry eye disease

Bose

Lee

Hou

et al. 2017

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tissue resident memory T cells in the human conjunctiva and immune signatures in human dry eye disease

Bose

Lee

Hou

et al. 2017

Sci Rep

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“…Amongst CD3 + T cells, effector memory T cells predominate in the human ocular surface. In earlier experiments, it has also been shown that CD8 + memory cells are the major populations in the conjunctival epithelial T cells among the healthy individuals 20 . Figure 3 shows that CD4 + and CD8 + effector memory T cells (T EM and T EMRA ) are the major subset in the human ocular surface in 10 healthy controls studied.…”

Section: Representative Resultsmentioning

confidence: 91%

“…The compensation was performed by testing PBMCs initially according to the protocol mentioned in Williams et al . 20 For testing, PBMCs were incubated with the same set of antibodies used here and compensated by comparing single and multiple antibody stains.…”

Section: Protocolmentioning

confidence: 99%

A Non-invasive Way to Isolate and Phenotype Cells from the Conjunctiva

Bose

Hou

Lee

et al. 2017

JoVE

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Traditionally, ocular surface cytology is studied with techniques such as spatula technology and brush technology. The problem with these techniques is that they may induce traumatic lesions on the surface of the eye, which can progress to scarring, eyelid deformity, limbal stem cell deficiency and in some cases, cause great discomfort to the subject. To avoid these clinical problems, impression cytology (IC) was developed to diagnose dry eye disease and later neoplasia, atopic disease, vernal keratoconjunctivitis and keratoconjunctivitis sicca. Typically, clinicians manually cut filter papers into required shapes and apply these to the ocular surface. Here, we describe how to perform IC using a commercially available medical device. This technique is explained here followed by immunophenotyping by flow cytometry. This technique requires less manual handling and causes less injury to the ocular surface.

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“…Ocular surface impression cytology is a simple minimally invasive test currently used in clinical practice for the diagnosis of limbal epithelial stem cell failure. 13 When adhered cells are recovered and analyzed by multicolor flow cytometry (OSIC-flow), 14 – 16 the technique provides a means to characterize the ocular mucosal cellular response associated with progressive conjunctival fibrosis and identify cellular subsets that may be associated with disease activity and progressive fibrosis when clinical evidence of inflammation has subsided.…”

mentioning

confidence: 99%

Conjunctival Neutrophils Predict Progressive Scarring in Ocular Mucous Membrane Pemphigoid

Williams

Southworth

Denniston

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeOcular mucous membrane pemphigoid (OcMMP) is a rare autoimmune disorder resulting in progressive conjunctival fibrosis and ocular surface failure leading to sight loss in up to 50%. This study was designed to optimize an ocular surface sampling technique for identification of novel biomarkers associated with disease activity and/or progressive fibrosis.MethodsFifty-seven patients with OcMMP underwent detailed examination of conjunctival inflammation and fibrosis using fornix depth measurement. Ocular surface impression cytology (OSIC) to sample superior bulbar conjunctiva combined with flow cytometry (OSIC-flow) profiled infiltrating leukocytes. Profiles were compared with healthy controls (HC) and disease controls (primary Sjögren's syndrome, pSS). Thirty-five OcMMP patients were followed every 3 months for 12 months.ResultsOverall neutrophils were elevated in OcMMP eyes when compared to pSS or HC (109 [18%] neutrophils/impression [NPI]; 2 [0.2%]; 6 [0.8%], respectively [P < 0.0001]) and in OcMMP patients with no visible inflammation when compared with HC (44.3 [7.9%]; 5.8 [0.8%]; P < 0.05). At 12 months follow-up, 53% of OcMMP eyes progressed, and this was associated with baseline conjunctival neutrophilia (P = 0.004). As a potential biomarker, a value of 44 NPI had sensitivity, specificity, and positive predictive values of 75%, 70%, and 73%, respectively. Notably, eyes with no visible inflammation and raised conjunctival neutrophils were more likely to progress and have a greater degree of conjunctival shrinkage compared to those without raised neutrophils.ConclusionsThese data suggest that OSIC-flow cytometric analyses may facilitate repeated patient sampling. Neutrophils may act as a biomarker for monitoring disease activity, progressive fibrosis, and response to therapy in OcMMP even when the eye appears clinically uninflamed.

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Cytokine Production and Antigen Recognition by Human Mucosal Homing Conjunctival Effector Memory CD8+ T Cells

Abstract: These data demonstrate that the majority of conjunctival epithelial CD8(+) T cells are mucosal homing αEβ7(+) effector memory T cells, which can recognize viral epitopes and are capable of secreting Granzyme B and IFN-γ.

Cited by 7 publications

References 38 publications

Tissue resident memory T cells in the human conjunctiva and immune signatures in human dry eye disease

Tissue resident memory T cells in the human conjunctiva and immune signatures in human dry eye disease

A Non-invasive Way to Isolate and Phenotype Cells from the Conjunctiva

Conjunctival Neutrophils Predict Progressive Scarring in Ocular Mucous Membrane Pemphigoid

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