Suppression of hematopoietic support function is associated with over-expression of IL-4 and TGF beta 1 in LP-BM5 MuLV infected stromal cell line

Murine acquired immunodeficiency syndrome (MAIDS) induced by defective LP-BM5 MuLV murine leukemia virus is a disease with many similarities to human AIDS. Our previous studies demonstrated the depressed hematopoiesis observed in LP-BM5 MuLV infected marrow cultures was attributed to a defective hematopoietic stroma. We report now the generation of permanent stroma cell fines from non-infected and LP-BM5 MuLV infected marrow cultures. Retrovirus infection was confirmed by polymerase chain reaction for detection of viral genome expresson, p12 envelope glycoprotein. The ability of these cell lines to support in vitro hematopoiesis was evaluated. The results demonstrated when cocultured with normal or infected nonadherent mononuclear cells, noninfected cell lines efficiently supported the production of hematopoietic progenitors, whereas virus-infected cell lines induced suppresson of both normal and virus-infected progenitors. Expression of cytokine genes in stromal cell lines was also examined. All cell lines expressed equivalent levels of transcripts for IL-1 beta, IL-2, IL-3, IL-6, IL-7, IL-IO, IFN, TNF-alpha, stem cell factor (SCF). However, infection was associated with higher expression of IL-4 and TGF beta 1. These findings demonstrate that infected stromal cell lines generate a defective hematopoietic microenvironment that produces altered cytokine expression resulting in faulty hematopoiesis. Further characterization of these defective cell lines should assist in the elucidation of the mechanism(s) whereby retrovirus produce altered hematopoiesis ultimately leading to the generation of immunodeficiency.