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Cutting Edge: Multiple Autoimmune Pathways in kd/kd Mice

Wayne W. Hancock, Tsai-Lung Tsai, Michael P. Madaio and David L. Gasser
J Immunol September 15, 2003, 171 (6) 2778-2781; DOI: https://doi.org/10.4049/jimmunol.171.6.2778
Wayne W. Hancock
*Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia and the University of Philadelphia School of Medicine, and Departments of
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Tsai-Lung Tsai
†Genetics and
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Michael P. Madaio
‡Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
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David L. Gasser
†Genetics and
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    FIGURE 1.

    Histological and immunopathologic features of renal disease in B6.kd mice. a, Severe interstitial inflammation and cystic dilatation with proliferative glomerulonephritis in a B6.kd mouse at 184 days of age, near end-stage renal disease (H&E-stained paraffin section). b–e, Immunohistological analysis of the cellular infiltrates in the kidneys of a RAG-1−/− kd/kd mouse at 150 days of age, showing lack of staining with an isotype control mAb (b), absence of TCR+ T cells (c), but marked infiltration by CD11b+ macrophages (d) and DX5+ NK cells (e) (cryostat sections, hematoxylin counterstain). f–I, Evaluation of the onset of tubular injury and apoptosis using a mAb to activated caspase-3, showing lacking of staining of a kidney from a 73-day-old control B6 mouse using control mAb (f) or anti-activated caspase-3 mAb (g), whereas a kidney from a 78-day-old B6.kd mouse shows lack of staining with a control mAb (h), but focal tubular labeling (i; arrowheads) for activated caspase-3. Immunohistological data are in each case representative of five kidneys examined from each group at the specified time point; all panels are ×250 original magnification.

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    Table I.

    Disease phenotypes in mutant and control strains

    GenotypeNo. Positive/Total Dissected
    Days 75–99Days 100–120Day >120
    B6NDa0/30/11
    B6.kdb1/1113/1934/37
    CD4−/−kd/kd1/41/422/26
    CD8−/−kd/kdND8/1013/17
    CD28−/−kd/kdND3/1941/62
    IL-2−/−kd/kd4/92/2ND
    Rag-1−/−kd/kd4/87/721/27
    ICAM-1−/−kd/kd0/21/223/23
    β2m−/−kd/kd0/22/28/15
    • a ND, Not done.

    • b The B6.kd mice in this table were from at least the eighth generation of backcrossing.

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    Table II.

    Composition of leukocytic infiltrates in mutant mice at ≥200 daysa

    B6.kdCD4−/− kd/kdCD8−/−kd/kdRag−/−kd/kd
    CD45+Diffuse infiltrate with peritubular aggregates 61.6 ± 8.8 cells/HPFDiffuse infiltrate with peritubular aggregates 58.2 ± 7.3 cells/HPFDiffuse infiltrate with peritubular aggregates 64.5 ± 9.2 cells/HPFDiffuse infiltrate with peritubular aggregates 31.2 ± 4.6 cells/HPFb
    T cells10–20% of infiltrate10–20% of infiltrate10–20% of infiltrateNegative
    CD410–20% of infiltrateNegative10–20% of infiltrateNegative
    CD81–5% positive10–20% of infiltrateNegativeNegative
    IL-2R1–5% positive<1% positive1–5% positiveNegative
    Mφ>75% leukocytes>75% leukocytes>75% leukocytes∼50% leukocytes
    NK∼10% leukocytes∼10% leukocytes∼10% leukocytes∼50% leukocytes
    ICOS5–10% of infiltrate∼10–20% of infiltrate1–5% of infiltrateNegative
    • a Assessed in three to four kidneys/group; HPF, high power field; CD45+ cells determined in six consecutive fields/sample (mean ± SD);

    • b , p < 0.01 vs infiltrates in each of the other three groups listed (t test); additional semiquantitative assessment <1%, 1–5%, 5–10%, 10–20%, 20–50%, 50–75%, or >75%.

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The Journal of Immunology: 171 (6)
The Journal of Immunology
Vol. 171, Issue 6
15 Sep 2003
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Cutting Edge: Multiple Autoimmune Pathways in kd/kd Mice
Wayne W. Hancock, Tsai-Lung Tsai, Michael P. Madaio, David L. Gasser
The Journal of Immunology September 15, 2003, 171 (6) 2778-2781; DOI: 10.4049/jimmunol.171.6.2778

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Cutting Edge: Multiple Autoimmune Pathways in kd/kd Mice
Wayne W. Hancock, Tsai-Lung Tsai, Michael P. Madaio, David L. Gasser
The Journal of Immunology September 15, 2003, 171 (6) 2778-2781; DOI: 10.4049/jimmunol.171.6.2778
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