Vasculitis in the Palmerston North mouse model of lupus - Phenotype and cytokine production profile of infiltrating cells

Objective. To define the phenotype of cells in the perivascular and vascula r infiltrates of Palmerston North (PN) mice and the cytokines that those ce lls produce. Methods. Immunohistologic analysis, flow cytometric analysis, and reverse t ranscriptase-polymerase chain reaction (RT-PCR) studies were performed on t issues and cells from female PN mice and age-matched and sex-matched DBA/2 mice. Results. With aging, PN mice developed a female-predominant, lupus-like dis ease, with a severe systemic mononuclear cell perivasculitis and vasculitis . The perivasculitis involved arteries and veins in kidney, liver, brain, a nd lung; the vasculitis predominantly involved veins and venules. The periv ascular and vascular infiltrates in female PN mice were composed mainly of an unusual cell type that expressed phenotypic markers characteristic of bo th T cells (Thy1+, CD3+, CD4+, T cell receptor + [TCR+]) and B cells (B220). In addition, the infiltrates contained a smaller number of conventional CD4+,B220- T cells and macrophages. Very few CD8+ T cells or surface Ig+ B cells were seen. Unlike the Thy1+,B220+ T cells present in MRL/lpr mice, mo st of which were CD4-,CD8- and TCR alpha/beta+, the majority of the Thy1+,B 220+ T cells in the perivascular/vascular infiltrates of PN mice were CD4and expressed either TCR alpha/beta or TCR gamma/delta. By immunohistologic staining, the cells in the perivascular and vascular infiltrates in the ki dneys of older PN mice were shown to produce interleukin-4 (IL-4), IL-6, an d IL-10, but not IL-2, interferon-gamma, transforming growth factor beta, t umor necrosis factor alpha, or IL-1 beta. By RT-PCR, the kidneys of older P N mice were found to express high levels of IL-4, IL-6, and IL-10 messenger RNA. Conclusion. The vascular and perivascular infiltrates in PN mice are compos ed predominantly of an unusual subpopulation of T cells that are Thy1+,B220 +,CD4+,CD8-, express either TCR alpha/beta or TCR gamma/delta, and produce mainly type 2 cytokines. The exact role of these cells in the immunopathoge nesis of lupus-like disease in PN mice remains to be elucidated.