Degree of CD4+ T Cell Recruitment Correlates With Clinical Presentation in Granulomatous Anterior Uveitis

Abstract

Abstract: : Purpose:CD4⁺ T cells are implicated in induction and development of granulomas. The aim of our study was to analyze the relative abundance of intraocular CD4⁺ T cells in aqueous humor and to compare infectious and non infectious granulomatous anterior uveitis by analyzing the phenotype of the accumulating T cells. Methods: Thirty patients presenting with unilateral or bilateral granulomatous anterior uveitis were included. Twelve of these cases had an infectious origin (ten with ocular toxoplasmosis and two with herpetic uveitis), thirteen had bilateral non infectious uveitis (nine with idiopathic uveitis and four associated with systemic sarcoidosis), and five had Fuchs heterochromic cyclitis with granulomatous features. Aqueous humor was obtained by paracentesis under topical anesthesia at the operating room. Intraocular T cells were analyzed by three–color flow cytometry using anti–CD4, anti–CD8, and anti–CD45RA mouse monoclonal antibodies. In each case, ocular T cell phenotypes were compared to those in peripheral blood collected on the same day. Results:Peripheral blood CD4⁺/CD8⁺ ratios were within normal ranges in all patients, contrary to intraocular CD4⁺/ CD8⁺ ratios. Virtually all intraocular CD4⁺ T cells were CD45RA negative. The ocular ratio was significantly higher in patients with sarcoidosis (13.6) than with idiopathic uveitis (4.00, p=0.005), toxoplasmosis (2.35, p=0.02), and Fuchs heterochromic cyclitis (1.30, p=0.01). The similar intraocular CD4⁺/CD8⁺ ratios were obtained in the two groups of granulomatous infectious uveitis showing similar aspect of keratic precipitates. Conclusions: CD4⁺ T cells represent the major intraocular T lymphocyte population in patients with granulomatous uveitis. The higher proportion of CD4 T cells population detected in aqueous humor as compared to peripheral blood suggests a specific recruitment of this population within the anterior chamber. Lack of CD45RA expression by intraocular CD4+ T cells further indicates recruitment of effector/memory cells and/or intraocular expansion with loss of CD45RA expression. A similar degree of CD4⁺ recruitment is associated with clinically identical keratic precipitates (i.e. sarcoidosis and idiopathic uveitis, versus herpetic or toxoplasmic uveitis). We postulate that clinical presentation of granulomatous uveitis is associated more with particular modalities of the immune response than with peculiar etiologies.

Keywords: uveitis-clinical/animal model • inflammation • anterior chamber