SUPPRESSION OF HEMATOPOIETIC SUPPORT FUNCTION IS ASSOCIATED WITH OVEREXPRESSION OF INTERLEUKIN-4 AND TRANSFORMING GROWTH-FACTOR-BETA-1 IN LP-BM5 MURINE-LEUKEMIA-VIRUS-INFECTED STROMAL CELL-LINES

Murine acquired immunodeficiency syndrome (MAIDS) induced by defective LP-BM5 murine leukemia virus (MuLV) is a disease with many similariti es to human AIDS, Our previous studies demonstrated that the depressed hematopoiesis observed in LP-BM5-infected marrow cultures could be at tributed to a defective hematopoietic stroma, We report now the genera tion of permanent stroma cell lines from noninfected and LP-BM5-infect ed marrow cultures, Retrovirus infection was confirmed by the polymera se chain reaction for detecting viral genome expression of the p12 env elope glycoprotein, The ability of these cell lines to support in vitr o hematopoiesis was evaluated. The results demonstrated that when cocu ltured with normal or infected nonadherent mononuclear cells, noninfec ted cell lines efficiently supported the production of hematopoietic p rogenitors, whereas in virus-infected cell lines production of both no rmal and virus-infected progenitors was suppressed, Expression of cyto kine genes in stromal cell lines was also examined, All cell lines exp ressed equivalent levels of transcripts for interleukin (IL)-1 beta, I L-2, IL-3, IL-6, IL-7, IL-10, interferon, tumor necrosis factor-alpha and stem cell factor, However, infection was associated with higher ex pression of IL-4 and transforming growth factor-beta 1, These findings demonstrate that infected stomal cell lines generate a defective hema topoietic microenvironment to produce altered cytokine expression and faulty hematopoiesis. Further characterization of these defective cell lines should assist elucidation of the mechanism(s) whereby retroviru ses alter hematopoiesis ultimately leading to the generation of immuno deficiency.