DIRECT EX-VIVO SIMIAN IMMUNODEFICIENCY VIRUS (SIV)-SPECIFIC CYTOTOXICACTIVITY DETECTED FROM SMALL-INTESTINE INTRAEPITHELIAL LYMPHOCYTES OFSIV-INFECTED MACAQUES AT AN ADVANCED-STAGE OF INFECTION

Human immunodeficiency virus (HIV) induces a profound disorganization of the lymphoid tissues with marked abnormalities of the immune system at the terminal stage of infection. Since the digestive mucosal immun e system is by far the largest lymphoid organ of the body, we attempte d to evaluate its functional activity in advanced stages of simian imm unodeficiency virus (SIV) infection in the SIV-macaque model of HIV in fection, Two chronically intravenously SIV-infected macaques, includin g one at the AIDS stage, were studied, Intestinal intraepithelial lymp hocytes (IEL) were isolated, analyzed, and compared to lymphocytes obt ained from blood, spleen, and different lymph nodes: IEL were predomin antly CD8(+) T lymphocytes expressing the alpha E beta 7 integrin and lacking the CD28 coactivatory molecule. A direct ex vivo SIV-specific cytotoxic activity was prominently found in the IEL of both macaques a nd was weaker or absent in the other sites, To our knowledge, this is the first report of SIV-specific cytotoxic activity from small intesti ne IEL in SIV-infected macaques. Considering the high similitude of th e SIV-macaque model with the HIV infection in humans, these results ma y be highly important for the pathogenesis of HIV infection and more g enerally important for the characterization and function of digestive CD8(+) IEL population.