Regulation of bovine leukemia virus tax and pol mRNA levels by interleukin-2 and-10

Recently, particular cytokines have been identified to affect progression o f a variety of diseases and retrovirus infections. Previously, we demonstra ted that interleukin-2 (IL-2), IL-12, and gamma interferon increased in per ipheral blood mononuclear cells (PBMCs) from animals with early disease and decreased in PBMCs from animals with late disease stages of bovine leukemi a virus (BLV) infection, In contrast, IL-10 increased with disease progress ion. To examine the effects of these cytokines on BLV expression, BLV tax a nd pol mRNA and p24 protein were quantified by competitive PCR and immunobl otting, respectively. IL-10 inhibited BLV tax and pal mRNA levels in BLV-in fected PBMCs; however, the inhibitory effect of IL-10 was prevented in PBMC s depleted of monocytes and/or macrophages (monocyte/macrophages). To deter mine whether these factors were secreted or monocyte/macrophage associated, monocyte/macrophage-depleted PBMCs were cultured with isolated monocyte/ma crophages in transwells where contact between monocyte/macrophages and nona dherent PBMCs was blocked. BLV tax and pal mRNA levels increased in transwe ll cultures similar to cultures containing nonseparated cells, and IL-10 ad dition inhibited the increase of BW tax and pal mRNA. These results suggest that monocyte/macrophages secrete soluble factor(s) that increases BLV mRN A levels and that secretion of these soluble factor(s) could be inhibited b y IL-10, In contrast, IL-2 increased BLV tax and pal mRNA and p24 protein p roduction, Thus, IL-10 production by BLV-infected animals with late stage d isease may serve to control BLV mRNA levels, while IL-2 may increase BLV mR NA in the early disease stage. To determine a correlation between cell prol iferation and BLV expression, the effect of IL-2 and IL-10 on PBMC prolifer ation was tested. As anticipated, IL-2 stimulated while IL-10 suppressed an tigen-specific PBMC proliferation. The present study, combined with our pre vious findings, suggests that increased IL-10 production in late disease st ages suppresses BLV mRNA levels, while IL-2-activated immune responses stim ulate BLV expression by BLV-infected B cells.