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

Objective: 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). Design: A cross-sectional comparative investigation of seven different mucosal sites from chronically SIV-infected rhesus monkeys was performed by analyzing blood and mucosal lymphocytes. Methods: 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. Results: 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. Conclusion: 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.