INCREASED NUMBERS OF GRANZYME-B-EXPRESSING CYTOTOXIC T-LYMPHOCYTES INTHE SMALL-INTESTINE OF HIV-INFECTED PATIENTS

The objective of this study was to determine whether granzyme B-expres sing cells, which identify activated cytotoxic lymphocytes, are presen t in the small intestinal mucosa of human immunodeficiency virus (HIV) -infected patients with and without diarrhea. Therefore, duodenal biop sy specimens from 29 HIV-infected patients (11 with diarrhea and 18 wi thout diarrhea) and 15 control patients were stained for the presence of granzyme B expressing cells. In HIV-infected patients, a significan tly increased expression of granzyme B in the lamina propria was obser ved (p = 0.00001): In 22 of 29 patients, at least 5-10 cells per high- power field were counted. In contrast, in 13 of 15 control patients, g ranzyme B was not expressed or minimally so, and in two others a maxim um of five granzyme-B-expressing cells could be detected per high-powe r field, No significant difference was found between the HIV-infected patients with and without diarrhea. Double staining revealed that the granzyme-B-expressing cells were mainly CD3 positive. These data shaw that activated cytotoxic T lymphocytes (CTLs) are present in the duode nal mucosa of HIV-infected patients. No relation between the number of CTLs and the presence of diarrhea was demonstrated. CTLs are known to be involved in the pathogenesis of HIV infection and in the productio n of tissue injury, but their functional role in intestinal HIV-relate d pathology has yet to be elucidated.