Assessment and diagnostic utility of the cytotoxic T-lymphocyte phenotype using the specific markers granzyme-B and TIA-1 in esophageal mucosal biopsies.

Most esophageal intraepithelial lymphocytes (IELs) express T-cell markers. Increased numbers of esophageal IELs have been shown in reflux esophagitis. The cytotoxic potential and activity of esophageal IELs have not as yet been examined. Our objectives were to determine whether esophageal IELs express the recently described cytotoxic T-cell (CTLs) markers, TIA-1 and granzyme-B, and whether the number of CTLs correlates with well-defined endoscopic, clinical, and histological features of esophagitis. In this study, most CD-3+ esophageal IELs exhibit the CD-8+/TIA-1+ T cell with cytotoxic potential phenotype in both histologically normal biopsy specimens and in biopsy specimens with esophagitis. A subpopulation of esophageal IELs that express cytotoxic activity was identified by granzyme-B immunostaining. A significant positive association was found between the number of esophageal IELs seen by light microscopy in biopsy specimens with histological features of reflux (21 IELs/HPF) and Candida esophagitis (31 IELs/HPF) as compared with normal-appearing biopsy specimens (10 IELs/HPF) (P< or =.05). Furthermore, the number of TIA-1 or granzyme-B-positive IELs were significantly increased in biopsy specimens with reflux esophagitis (34 and 15 cells/HPF) and Candida esophagitis (44 and 18 cells/HPF) as compared with normal (11 and 2 cells/HPF) (P< or =.05). Granzyme-B and CD-3-positive IELs were also significantly elevated in biopsy specimens with reflux-associated squamous hyperplasia (P< or =.05). Finally, biopsy specimens of patients with dysphagia and to a lesser extent dyspepsia/heartburn exhibited increased numbers of IELs bearing the cytotoxic phenotype when compared with asymptomatic patients. In conclusion, we provide immunohistochemical evidence that most esophageal IELs exhibit the cytotoxic phenotype and that activated cytotoxic IELs are increased in reflux and Candida esophagitis.