Mucosal immunodeficiency in HIV/SIV infection

The gastrointestinal tract is one of the major target organs for secondary infections and malignancies in HIV infection in humans indicating disturbed local immunologic defense mechanisms. Immunohistology and flow cytometric studies have demonstrated a more pronounced loss of CD4+ T cells in the intestinal mucosa compared to the peripheral blood in humans infected with HIV. In parallel, activated CD8+ T cells in the lamina propria are increased in this compartment. In SIV-infected nonhuman primates a very early loss of CD4+ T cells in the intestinal mucosa compared to the peripheral blood occurs already at 2 weeks after infection. Depletion and functional impairment of mucosal CD4+ T lymphocytes with consecutive altered cytokine secretion in HIV/SIV infection may explain the breakdown of the mucosal immune barrier leading to secondary opportunistic or nonopportunistic infections and secondary malignancies. In addition, due to the interrelation between the mucosal immune system and epithelium, these changes might be responsible for the partial small intestinal mucosal atrophy and maturational defects in enterocytes observed in HIV-infected patients.