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 be en examined. Our objectives were to determine whether esophageal IELs expre ss the recently described cytotoxic T-cell (CTLs) markers, TIA-I and granzy me-B, and whether the number of CTLs correlates with well-defined endoscopi c, 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 b iopsy specimens with esophagitis. A subpopulation of esophageal IELs that e xpress cytotoxic activity was identified by granzyme-B immunostaining. A si gnificant positive association was found between the number of esophageal I ELs seen by light microscopy in biopsy: specimens with histological feature s of reflux (21 IELs/HPF) and Candida esophagitis (31 IELs/HPF) as compared with normal-appearing biopsy specimens (10 IELs/HPF) (P less than or equal to .05). Furthermore, increased in biopsy specimens with reflux esophagiti s (34 and 15 cells/HPF);md Candida esophagitis (44 and 18 cells/HPF) as com pared with normal (11 and 2 cells/HPF) (P less than or equal to .05). Granz yme-B and CDS-positive IELs were also significantly elevated in biopsy spec imens with reflux-associated squamous hyperplasia (P less than or equal to .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. Copyright (C) 1999 by W.B. Saunders Compan y.