T cells expressing the T-cell receptor (TCR) gamma delta home in on various epithelia and may play an important role in local immunity to foreign antigens. The nasal mucosa is a potential site for chronic inflammatory diseases, yet little is known about the characteristics of nasal mucosal gamma delta T cells. Using flow cytometry, immunohistochemistry, and RT-PCR, we elucidated the characteristics of nasal mucosal gamma delta T cells in patients with perennial allergic rhinitis (PAR), chronic infective rhinitis (CIR), and seasonal allergic rhinitis (SAR) and in normal subjects. The gamma delta T cells were significantly increased in the nasal mucosa of patients with PAR (PAR, 24.3 +/- 4.5%; CIR, 12.9+/- 2.7%, p < 0.01), unrelated to those in autologous peripheral blood (PAR, 5.6 +/- 0.8%; CIR, 9.6 +/- 2.8%), and they were preferentially distributed in the epithelial compartment (26.7 +/- 2.3%) rather than in the lamina propria (5.4 +/- 2.5%). Of the expanded population of nasal mucosal gamma delta T cells in patients with PAR, CD4+ and CD4-8- gamma delta T cells were selectively increased (p < 0.01). Although nasal intraepithelial gamma delta T cells from all groups of patients and normal subjects dominantly expressed the V gamma 1/V delta 1 genes, and a bias for V gamma 3 gene expression was noted in those of patients with PAR, a significantly larger fraction of nasal mucosal gamma delta T cells in patients with PAR expressed the V gamma 1/V delta 1 TCR (p, 0.01), whereas those of the peripheral blood expressed the V gamma 2/V delta 2 TCR. More than 60% of V gamma 1/V delta 1 TCR+ cells in patients with PAR, were CD45RO+ ("memory cells"), independent of those in their peripheral blood (p < 0.01). Furthermore, a substantial proportion of nasal mucosal gamma delta T cells in patients with PAR synthesized IL-4 and IL-5 but negligible amounts of IFN-gamma. These observations of an increase in the proportions and activation of distinct subsets of nasal mucosal gamma delta T cells and their Th2-type cytokine profile in patients with PAR, unrelated to those in autologous peripheral blood suggest an important role for the oligoclonally expanded expanded nasal mucosal gamma delta T cells in the pathogenesis of PAR.