Induction of Colitis and Exocrinopathy in Nude Mice Induced by Immunocompetent Cell Transfer from Murine Retrovirus-lnfected Mice

Abstract

LP-BM5 murine leukemia virus (MuLV) is known to induce murine acquired immunodeficiency syndrome (MAIDS). We have shown that Sjogren syndrome (SS)-like exocrinopathy can be induced in mice with MAIDS and that adoptive transfer of immunocompetent cells of MAIDS mice can induce inflammatory bowel disease (IBD)-like colitis, which we termed “MAIDS colitis,” and exocrinopathy in recipient syngeneic nude mice. To identify which phenotype of cells in MAIDS induces colitis and exocrinopathy in our model, we analyzed adoptive transfer of separated cell fraction into nude mice. LP-BM5 MuLV was inoculated in 4-week-old C57BL/6 (B6) mice intraperitoneally. Eight weeks after infection, lymph node cells from the virus-infected mice were separated into three fractions using magnetic beads as follows: group 1, whole lymph node cells; group2, CD4+ T cells; group3, non-T, non-B (Mac-1+) cells. Each fraction was transferred to B6 nude mice. Four to six weeks after cell transfer the mice were killed and their tissues analyzed histopathologically. All of the mice inoculated with MAIDS lymph node cells (group 1) exhibited colitis and systemic exocrinopathy, and they died within 6 weeks after cell transfer. Transfer of the CD4+ fraction (group 2) induced exocrinopathy but not colitis. Transfer of the non-T, non-B (Mac-1+) cell fraction (group 3) induced colitis but not exocrinopathy. Mac-1+ macrophages and CD4+ T cells of mice with MAIDS play a distinct role in the development of organ-specific autoimmune-like lesions (i.e., ulcerative colitis-like colitis and SS-like exocrinopathy, respectively).