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

• Published in: Arthritis and rheumatism 1999-03, Vol.42 (3), p.561-568
• Main Authors: Luzina, Irina G., Knitzer, Robert H., Atamas, Sergei P., Gause, William C., Papadimitriou, John C., Sztein, Marcelo B., Storrer, Catherine E., Handwerger, Barry S.
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - immunology; Biological and medical sciences; Disease Models, Animal; Female; Gene Expression - immunology; Interferon-gamma - genetics; Interleukin-1 - genetics; Interleukin-10 - genetics; Interleukin-2 - genetics; Interleukin-4 - genetics; Interleukin-6 - genetics; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Medical sciences; Mice; Mice, Inbred DBA; Mice, Inbred MRL lpr; Mice, Inbred NZB; Mice, Inbred Strains; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T-Lymphocytes - immunology; Transforming Growth Factor beta - genetics; Vasculitis - genetics; Vasculitis - immunology
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/1529-0131(199904)42:3<561::AID-ANR22>3.0.CO;2-X

Objective To define the phenotype of cells in the perivascular and vascular infiltrates of Palmerston North (PN) mice and the cytokines that those cells produce. Methods Immunohistologic analysis, flow cytometric analysis, and reverse transcriptase–polymerase chain reaction (RT‐PCR) studies were performed on tissues 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 disease, with a severe systemic mononuclear cell perivasculitis and vasculitis. The perivasculitis involved arteries and veins in kidney, liver, brain, and lung; the vasculitis predominantly involved veins and venules. The perivascular and vascular infiltrates in female PN mice were composed mainly of an unusual cell type that expressed phenotypic markers characteristic of both 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, most of which were CD4−,CD8− and TCRα/β+, the majority of the Thy1+,B220+ T cells in the perivascular/vascular infiltrates of PN mice were CD4+ and expressed either TCRα/β or TCRγ/δ. By immunohistologic staining, the cells in the perivascular and vascular infiltrates in the kidneys of older PN mice were shown to produce interleukin‐4 (IL‐4), IL‐6, and IL‐10, but not IL‐2, interferon‐γ, transforming growth factor β, tumor necrosis factor α, or IL‐1β. By RT‐PCR, the kidneys of older PN 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 composed predominantly of an unusual subpopulation of T cells that are Thy1+,B220+,CD4+,CD8−, express either TCRα/β or TCRγ/δ, and produce mainly type 2 cytokines. The exact role of these cells in the immunopathogenesis of lupus‐like disease in PN mice remains to be elucidated.