Accumulation of Th-2-like helper T cells in the conjunctiva of patients with vernal conjunctivitis

Abstract

A total number of 132 T cell clones (TCC) were obtained by PHA-stimulation of single T cells from mononuclear cell suspensions of conjunctival flogistic infiltrates of three patients with vernal conjunctivitis (VC). The phenotype and functional properties of these TCC were compared with those of 122 TCC contemporarily established from PB mononuclear cell suspensions of the same patients, 120 TCC established from lymph nodes of three patients with nonspecific hyperplastic lymphoadenitis and 159 TCC established from thyroid lymphocyte infiltrates of three patients with Graves’ disease. The great majority of conjunctival TCC displayed the CD4+ CD8- phenotype (CD4/CD8 ratios ranging from 6.1 to 7.0), whereas the mean CD4/CD8 ratios for control TCC ranged from 0.9 to 2.4. After stimulation with either PHA or PMA plus anti-CD3 mAb, conjunctival TCC differed from control TCC for their ability to produce cytokines. In particular, a large number of conjunctival TCC produced IL-4, but no, or limited amounts of, IFN-gamma, whereas no difference was observed between conjunctival and control TCC with regard to the production of IL-2. The failure of IFN-gamma production by conjunctival TCC was apparently not caused by delay or block in cytokine production, but actually reflected the lack of IFN-gamma transcription. Virtually all conjunctival TCC able to produce IL-4, but not IFN-gamma, as well as most of those producing both cytokines, provided helper function for IgE synthesis in allogeneic normal B cells. The accumulation in the conjunctiva of patients with vernal conjunctivitis of CD4+ T cells that, apart from the production of IL-2, resembles murine Th2 cells for their profile of cytokine production and helper function suggests a possible role for these cells in the pathogenesis of the disease.