The Situation Of HIV Infection And Changes Of Local Immune Function In Gastro-mucosal Tissues From The Patients With AIDS Or Pre-clinical HIV Infection

Objective: Mucosa associated lymphoid tissue (MALT) is one of the main site in which CD4~+ T cells are located. Reserching on the changes of mucosal CD4~+ T cells and local immune function during HIV infection will help us better understand the mechanism of HIV infection and AIDS, and suggest novel potential therapeutic strategy in clinical settings. The present study was performed using gastro-mucosal tissues from HIV infection patients to explore the changes of CD4~+ T cells, CD8~+ T cells, NK cells, B cells and their immune activation, which could have important implications in terms of mechanisms of HIV infection and pathogenesis.Methods: Gastro-mucosal tissues of HIV patients were prepared from autopsy and biopsy under gastroscope, in turns 10% buffer formalin fixing and paraffin imbedding. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect HIV in gastro-mucosal tissues of HIV infection patients. Meanwhile, the distribution and quantity of immunocytes, including CD3~+ T cells, CD4~+ T cells, CD8~+ T cells, NK cells and B cells, were performed with IHC method to discuss the influence of HIV infection on immunocytes and innate immunity of gastro-mucosal tissues. In addition, we observed the expression of CD38 and Ki-67 in gastro-mucosal tissues of HIV patients to expound alterations of immunoproliferating and activation by using IHC. Subsequently, the infection of helicobacter pylori (Hp) was checked in gastro-mucosal tissues of HIV patients with silver staining and IHC. At last, collagen deposition in gastro-mucosal tissues of HIV patients was estimated with Masson's trichromatic staining.Result: 1. The situation of HIV infection in gastro-mucosal tissues: (1) Our study found HIV gag sequence in not only CD4~+ T cells but also mucosalepithelial cells, gland epithelial cells in lamina propria and spindle stromal cells; (2) HIV p24 was expressed in T cells, plasmocyte, and a few mucosa epithelial cells, gland epithelial cellls and dell epithelial cellls. 2. Comparing with control group, CD4~+ T cells of AIDS patient were markedly depleted in gastro-mucosal tissues(P＜0.01), but in presymptomatic patients CD4~+ T cells were not significantly different. CD3~+ T cells, CD8~+ T cells and NK. cells were notably increased (P<0.01), and they severely infiltrated glands and epitheliums in gastro-mucosal tissues. And the quantity and distribution of CD20~+ B cells between patients and control group were not obviously different. 3. 14 of 42 patients infected Hp, and total infection ratio was 33.3% which was higher than control group (P＜0.01), the infection ratio in presymptomatic HIV infection group was 50% which was the highest among them. 4. Comparing with control group, the expression of Ki-67 was markedly down-regulated (P<0.01), while the expression of CD38 was markedly up-regulated (P＜0.01). 5. Collagen deposition was noted in stroma and folliculus lymphaticus of gastro-mucosa tissues. Conclusions:1. In gastro-mucosal tissues from HIV infection patients, HIV could infect not only CD4~+ T cells but also mucosal, gland epithelial cells and dell epithelial cells, as well as a few stroma cells, which suggested that gastro-mucosa is an infected site of HIV infection,and mucosal and gland epithelial cells are target cells of HIV infection.2. There are different degree of inflammatory reaction, stroma proliferation, glandular and mucosal epithelial degeneration, apoptosis, and atrophy of folliculus lymphaticus in gastro-mucosa.3. CD4~+ T cells in gastro-mucosa of AIDS patients were markedly decreased. The numbers of CD3~+ T cells, CD8~+ T cells, NK cells and so on were relatively increased, which cells severely infiltrated the glands and epitheliums in gastro-mucosa of HIV infection. However distinctions of CD20~+ B cells in number and distribution between HIV infection and control subjects was not noted. These changes imply that the alteration of CD4~+ T cells and local immune homeostasis induced by HIV infection could result in aggregation of CD8~+ T cellsand NK cells in local gastro-mucosa. CD8~+ T cells and NK cells infiltrating the glands and epitheliums in lamina propria could be associated with HIV infecting mucosal and gland cells. The state of CD8~+ T cells, NK cells and B cells in HIV infection gastro-mucosa shows that cell immunity and innate immunity are predominantly influenced rather not humoral immunity during HIV infection.4. Hp infection ratio in HIV infection patients was increased, especially in presymptomatic HIV infection group, which suggested the changes of local mucosa immunocytes in function might be more obviously influence than in number in HIV infection.5. According to the result of down-regulated expression of Ki-67 and up-regulated expression of CD38 and collagen deposition, we could infer that HIV infection could lead to unbalance of lymphocyte regeneration and immune phenotype activation, which might result in the depletion of immune system, and lead to breakdown of MALT structure.