Mucosal Atrophy Is Associated with Loss of Activated T Cells in the Duodenal Mucosa of Human Immunodeficiency Virus (HΙV)-Infected Patients

Abstract

Gastrointestinal symptoms and malabsorption are frequent in HIV-infected patients even in the absence of opportunistic infections. In earlier studies we found indications that the gastrointestinal mucosa itself may be affected by HIV. Since there is evidence that the mucosal structure is influenced by changes in the gut-associated lymphoid tissue, we have investigated mucosal structure and immune cells in HIV-infected patients. Sixty patients (3 f, 57 m; age 21–61, median 37 years; 11 at CDC stage II or III, 49 at stage IV) with gastrointestinal complaints undergoing upper endoscopy were examined for enteric pathogens. Duodenal biopsies were labelled by immunohistology for HIV antigen p24 and for lymphocyte surface markers; mucosal architecture was studied by three-dimensional morphometry. Biopsies from HIV seronegative patients without abnormal findings served as controls. In 29 patients an enteric pathogen was identified. In 22 patients HIV-infected mononuclear cells were detected in the lamina propria. In the lamina propria CD25⁺ cells were decreased, CD3⁺ and CD8⁺ cells were increased in HIV-infected patients compared with controls, while the numbers of CD4⁺, Leu8⁺, and HML-1⁺ cells, and of macrophages were not different. Patients at stage IV had decreased numbers of CD4⁺ T cells compared with patients at stage II or III. Villus surface area was reduced in HIV-infected patients compared with controls. Crypt depth was increased in patients with intestinal infection compared with controls while numbers of mitotic figures were normal. Patients without intestinal infection and patients with mucosal HIV-infected cells had decreased numbers of mitotic figures and normal crypt depth compared with controls. The loss or functional impairment of activated helper T cells in the mucosa and increased suppressor activity may be responsible for the frequent occurrence of gastrointestinal infections and malignancies in HIV-infected patients. Furthermore, mucosal atrophy with hyporegeneration may also be due to the loss of activated regulatory T cells in the mucosa of HIV-infected patients.