Altered in vivo dynamics of corneal intraepithelial T cells and changes to corneal sensory nerves in HIV-positive individuals

Abstract

Purpose : HIV-infected individuals on antiretroviral therapy (ART) often achieve normalisation of T cell parameters in the circulation. Using Functional In Vivo Confocal Microscopy (Fun-IVCM), corneal immune cell subsets, including intraepithelial T cells and dendritic cells (DCs), and stromal macrophages, can be identified and their dynamic features evaluated in living humans. This study sought to investigate the corneal immune cell profile and sensory nerves in HIV+ ART+ patients compared to healthy controls.

Methods : HIV+ patients on ART treatment (n=16, 71±5 years) and age- and sex-matched non-HIV controls (n=15, aged 67±6) were recruited. Corneal Fun-IVCM imaging (Heidelberg HRT-3 with Rostock Module) was performed at 3-6 minute intervals for up to 6 timepoints. Time-lapsed videos were created using customised MATLAB scripts and the morphodynamics of corneal T cells, DCs and macrophages were analyzed manually in ImageJ. Corneal sensory nerve parameters were assessed using ACCMetrics. Cell density and nerve parameters were analyzed using t-test or Wilcoxon signed-rank test. Cell morphology and dynamics were analyzed by fitting mixed-effects models.

Results : HIV+ patients had a similar ocular surface status and corneal immune cell density as healthy controls. The morphology and dynamic behavior of intraepithelial DCs and stromal macrophages were also similar across the groups. However, T cells in HIV+ individuals had a higher trajectory speed than T cells in controls (1.51±0.53 vs 1.21±0.59 µm/min, p=0.025). The higher dynamic activity of T cells in the HIV+ group was also evidenced by a higher percentage of mobile T cells (speed > 2 µm/min) compared to the control group (67% vs 48%, p=0.002). In addition, a higher corneal nerve fiber width was observed in HIV+ individuals (0.022±0.001 vs 0.020±0.001, p=0.004).

Conclusions : This study reveals that the dynamic behavior of corneal intraepithelial T cells is altered in HIV+ individuals with continuing ART treatment. Further studies are warranted to investigate how the T cells in the cornea of HIV+ individuals function differently and their correlation with blood T cell profile. This study also highlights how Fun-IVCM can be used as a tool to assess corneal immune cell profiles in systemic disease, to identify potential biomarkers for immune-related diseases and conditions.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.