Correlation between CD4+ T-cell loss and Gag-specific T cells in different intestinal sites of chronically SIV-infected rhesus monkeys

Abstract

To determine the loss of CD4+ T cells and virus-specific cytotoxic T cells (CTL) in different mucosal sites of rhesus monkeys infected with simian immunodeficiency virus (SIV). A cross-sectional comparative investigation of seven different mucosal sites from chronically SIV-infected rhesus monkeys was performed by analyzing blood and mucosal lymphocytes. Mucosal lymphocytes were isolated from duodenum, jejunum, ileum and colon as well as from vagina, cervix and uterus of SIV-infected rhesus monkeys at necropsy. CD4+ T cells and SIV-Gag-specific CTL were determined in blood and mucosal samples by flow cytometry. A significant depletion of CD4+ T cells was observed in blood and all mucosal sites of SIV-infected rhesus monkeys compared to uninfected animals. But the mean percentage loss of CD4+ T cells varied between 66 and 95% between the different mucosal tissues. The frequency of CTL ranged between 0.4 and 2.4% with the highest proportions in vagina and cervix. Among the intestinal sites the mean levels of CTL correlated with mean percentage loss of CD4+ T cells. A discriminative pronounced loss of CD4+ T cells among the mucosal tissues confirmed that viral replication affects different mucosal sites in a distinct way. Despite high levels of CTL, especially in vagina and cervix, the severe loss of mucosal CD4+ T cells could not be prevented during chronic SIV infection. However, within the four sites of the intestine a high virus-specific cellular immune response correlated with better preservation of CD4+ T cells.