Immunomodulation in the Murine AIDS Model



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Murine acquired immunodeficiency syndrome (MAIDS) is a model of immunodeficiency useful for studying human AIDS. Murine leukemia virus (MuLV) produces a fatal disease course in some strains of mice with symptoms mimicking AIDS. BALB/c mice exhibit natural MAIDS resistance and suppress viral replication, while C57BL/6 mice cannot control viral replication and develop MAIDS. Identifying genes and proteins differentially expressed between strains may aid in defining a ‘successful’ immune response against MuLV. Candidate molecules for study include natural immunosuppressors that protect against strong, unnecessary immune responses. Overexpression of immunosuppressors may turn down immune responses necessary for eliminating viruses. Two natural immunosuppressors are indoleamine 2,3-dioxygenase (IDO) and interleukin-10 (IL-10). Immune activators including Type I (α/β) interferons may also be differentially expressed. This study compared the balance in immunosuppressive (IDO and IL-10) versus immune activating (IFN-α/β) molecules between BALB/c and C57BL/6 mice to elucidate relative levels of natural immunosuppression in MAIDS. Techniques used included RNA-based and protein-based assays. No significant differences were seen between strains in IFN-α/β expression, either at the mRNA or protein level. In contrast, results showed significant upregulation of IDO and IL-10 by disease-susceptible mice in the first week of infection. Immunosuppressor upregulation in MAIDS-susceptible mice may prevent effective T cell responses, predisposing susceptible mice towards developing MAIDS. Further study may delineate potential roles for IDO and IL-10 in human development of AIDS.