CELLULAR IMMUNE FUNCTION IN AIDS AND CANCER

HIV感染引起免疫调节细胞因子的改变

Immunoregulatory cytokine changes result from HIV infection, with decreased type 1 cytokines that enhance cellular immunity (CI) and increased type 2 cytokines that augment humoral immunity (HI). IL-12 and IL-10 enhance CI and HI, respectively, and are produced by monocytes/macrophages (M/M), important targets of HIV infection. M/M from HIV+ patients produced reduced levels of IL-12 and increased levels of IL-10, as did M/M infected in vitro with HIV. IL-12 p40 and p35 mRNA expression was reduced in advanced but not in asymptomatic patients. Therapeutic trials of pediatric AIDS patients with HIV protease inhibitors suggested that patients who presented with reduced viral loads and increased CD4 counts did not exhibit normalized IL-12 and IL- 10 production. This finding suggests that protease inhibitor-induced changes in CD4 count and viral load is not reflected in improved immune function. M/M from uninfected newborns of HIV-infected mothers do not produce IL-12, in contrast to the M/M of newborns of HIV uninfected mothers that do produce IL-12. HIV-induced cytokine dysregulation may be due to a reduction in signal transducers and activators of transcription (STATs), as T cells from HIV-infected patients as well as T cells infected in vitro with HIV-1 exhibited reduced levels of STAT5, but not of the other known STATs. Seronegative, HIV-exposed, T cell- responsive individuals exhibited a dominant type 1 cytokine profile when stimulated with HIV antigens, whereas HIV-infected individuals showed a dominant type 2 cytokine pattern. CD8+ T cell lines resulting from HLA alloantigen mixed lymphocyte stimulation generated a factor that blocked HIV infection of PHA stimulated autologous and allogeneic targets, and also inhibited CMV infection of human fibroblast cell lines. This alloantigen stimulated CD8 anti-viral factor does not appear to be any of the b-chemokines. The factor inhibited T-tropic, M-tropic, and primary isolates of HIV-1, as well as a chronically- infected cell line. Thus, this allo-stimulated factor is capable in vitro of blocking multiple HIV isolates, as well as one of the opportunistic viruses that is problematic in AIDS. AZT was incorporated into the fetal cord blood leukocytes from a majority of women who received AZT during pregnancy. Based on experience from a murine model, this finding raises the possibility of long-term AZT-induced carcinogenesis in the offspring. AIDS title: Immune Defects in HIV/AIDS.