Immunological changes in retrovirus-infected mice.

Abstract

Acquired Immune Deficiency Syndrome (AIDS), a progressive immunodeficiency induced by Human Immunodeficiency Virus (HIV), frequently sets the stage for life-threatening tumors and opportunistic infections. The proposed study focuses on the immunological changes associated with HIV infection. Often superimposed diarrhea, causing malabsorption and malnutrition, leads to further immunosuppression and accelerated deterioration in many patients. The pathomechanism of Cryptosporidium-induced diarrhea is poorly understood and its relation to AIDS urgently requires investigation. We used LP-BM5 murine leukemia virus (MuLV)-infected C57BL/6 mice to model AIDS and thereby study the immunological changes in human retrovirus infection. Production of Th1 cytokines (IL-2 and IFN-γ) was suppressed, whereas Th2 cytokine production (IL-4, IL-5, IL-6, and IL-10) was enhanced in spleen and mesenteric lymph nodes (MLN) during retrovirus infection. However, increased secretion of IFN-γ in the MLN of retrovirus-infected mice may represent incremental production and release by non-Th1 cells. Lymphoid cell population changes in gut-associated lymphoid tissues (GALT) were documented 4 months after retrovirus infection. Total lymphoid cell numbers decreased in Peyer's patches and CD4⁺ cell numbers decreased in the intestinal lamina propria (ILP). Total lymphoid cell numbers increased in MLN but the relative percentages of surface IgA⁺, cytoplasmic IgA⁺ (cIgA⁺), and cIgM⁺ cells were decreased. Cryptosporidium infestation in retrovirus-infected mice decreased following the administration of pooled bovine colostrum containing a high titer of antibody demonstrating the potential efficacy of passive humoral immunity. Changes in the host cellular immune apparatus, following Cryptosporidium infection, were as follows: (1) increased γδ-TCR⁺ cells in the ILP 6 and 10 days post-infection, (2) decreased CD4⁺ cells in the ILP and intraepithelium 10 days post-infection, (3) reduced IgA⁺ and IgG⁺ cells in the ILP 6 and 10 days post-infection, and (4) increased IgE⁺ cells 6 days post-infection. This altered cellular profile indicates the potential for aberrant cytokine production which may be responsible for the compounded immunodeficiency during retrovirus infection. Overall, the findings underscore the importance of understanding both humoral and cell-mediated immunological influences before the rational development of a therapy against opportunistic cryptosporidial infection in AIDS patients can be undertaken.