Oligoclonal activation of CD4+ T lymphocytes in posterior uveitis

Abstract

SUMMARY Several lines of evidence support an important role for activated T lymphocytes in the perpetuation of autoimmune intraocular inflammatory disease (posterior uveitis). In this study peripheral blood lymphocytes (PBL) were examined by three-colour flow cytometry to assess the distribution of IL-2 receptors (IL-2R) among CD4+ and CD8+ T cell subsets in patients with active posterior uveitis and control subjects. Patients with uveitis (n= 70) showed a significant increase in PBL expressing the α-chain (Tac) of the IL-2R compared with controls (n= 28) (34·2%versus 29·6%) (P < 0·05). This increased Tac expression was present on both the CD4+ subset (25·7%versus 20·9%) (P < 0·05) and the CD8+ subset (2·5%versus 1·8%) (P < 0·05) of lymphocytes. We also examined whether the activated CD4+ PBL from uveitis patients (n= 30) showed a dominant pattern of T cell receptor (TCR) gene rearrangement, suggestive of an oligoclonal response to a small number of antigenic peptides. A significant increase in the usage of the Vα2.3 TCR family by activated but not by non-activated CD4+ PBL was detected in patients (3·9%versus 3·4%) (P < 0·05) compared with controls. There was evidence of oligoclonal activation of CD4+ PBL in 11/30 patients (36·7%) but in none of the controls (n= 10). However, different Vα or Vβ TCR families were selectively activated among and even within individual patients. The heterogeneity in TCR expression among patients with active intraocular inflammatory disease is discussed.