The Role of αβ+ T Cells and Homeostatic T Cell Proliferation in Y-Chromosome-Associated Murine Lupus

Brian R. Lawson, Stefanos I. Koundouris, Marlene Barnhouse, Wolfgang Dummer, Roberto Baccala, Dwight H. Kono and Argyrios N. Theofilopoulos
J Immunol August 15, 2001, 167 (4) 2354-2360; DOI: https://doi.org/10.4049/jimmunol.167.4.2354

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Cumulative survival rates for littermate TCRα−/− and TCRα+/+ male BXSB mice (20 mice/group) followed for 9 mo.

  • FIGURE 2.
    FIGURE 2.

    Polyclonal (A) and antichromatin (B) IgG subclass levels in 5-mo-old TCRα−/− and TCRα+/+ littermate male BXSB mice. Data are the mean ± SEM of six to eight mice per group. Total polyclonal and antichromatin IgG are the sum of the four subclasses.

  • FIGURE 3.
    FIGURE 3.

    Glomerular pathology and immune complex IgG deposits in representative littermate 5-mo-old TCRα−/− and TCRα+/+ male BXSB mice. Upper panels, Periodic acid-Schiff-stained sections of paraffin-embedded tissues (original magnification, ×64). There is substantially less cellular proliferation and periodic acid-Schiff-staining deposits in the TCRα−/− glomeruli. Polymorphonuclear cells, which are unique to the glomerular lesions of the male BXSB mouse, can be readily seen. Lower panels, Direct IgG immunofluorescence of kidney sections (original magnification, ×32 at equal exposure).

  • FIGURE 4.
    FIGURE 4.

    Homeostatic proliferation of male and female WT BXSB CD4+ T cells transferred into male BXSB TCRα−/− recipients. A, Cell division analyzed by FACS on gated CFSE-stained CD4+Thy1.2+ T cells on days 5 and 21. The large population on the left represents donor cells that have undergone seven, eight, or more divisions and are, therefore, CFSE negative. B, Numbers of CD4+ donor T cells recovered from recipient’s LN and spleens. Data are from three mice per group at each time point and are representative of two separate experiments.

  • FIGURE 5.
    FIGURE 5.

    Cumulative survival rates for male BXSB TCRα−/− mice adoptively transferred with 4–5 × 106 CD3+ LN T cells from either male or female WT BXSB mice. Recipient mice (10–12 mice/group) were followed for up to 7 mo after transfer. The survival rate for a cohort of 20 unmanipulated WT male BXSB mice is depicted for comparison.

  • FIGURE 6.
    FIGURE 6.

    Polyclonal (A) and antichromatin (B) IgG subclass levels in male BXSB TCRα−/− mice at 7 mo after transfer of WT male or female BXSB CD3+ LN T cells. Comparisons are made with 4-mo-old unmanipulated male BXSB mice. Data are the mean ± SEM of six to eight mice per group. Total polyclonal and antichromatin IgG are the sum of the four subclasses.

Tables

  • Table I.

    Lymphoid organ weights and cellular subsets of BXSB TCRα−/− micea

    TCRαSpleen WeightLN WeightCD4+ SubsetCD8+ SubsetCD19+PBMC Mac-1+
    TotalCD44highTotalCD44high
    −/−0.2 ± 0.5b0.04 ± 0.01b1.2 ± 0.050.8 ± 0.0185.5 ± 0.9b8.9 ± 0.1b
    +/+0.4 ± 0.050.4 ± 0.0217.7 ± 1.584.9 ± 2.72.3 ± 0.381.2 ± 2.774.9 ± 1.421.2 ± 3.2

    • a CD4+, CD8+, and CD19+ are expressed as percentage of total splenocytes, CD44high as percentage of splenic CD4+ or CD8+ cells, and Mac-1+ as percentage of PBMC. LN (axillary, inguinal, cervical, and mesenteric) and spleen weights are in grams. Values are means ± SEM of six to eight mice per group at 5 mo.

    • b , p < 0.05 between knockout and WT mice.

  • Table II.

    Kidney disease in BXSB TCRα−/− micea

    TCRαKidney WeightGN ScoreBlood Urea NitrogenImmune Complex Deposit Score
    −/−0.2 ± 0.1b2.0 ± 0.1b1.5 ± 0.3b1.3 ± 0.3b
    +/+0.35 ± 0.053.5 ± 0.33.2 ± 0.33.5 ± 0.4

    • a Kidney weights (grams) and severity of GN, blood urea nitrogen, and immune complex IgG deposits graded on a 0–4 scale. Mean ± SEM of six to eight mice per group at 5 mo.

    • b , p < 0.05 between deleted and WT mice.

  • Table III.

    Lymphoid organ weights and cellular subsets in TCRα−/− male BXSB recipients of WT male or female CD3+ cells

    SpleenLNCD4+ SubsetsCD8+ SubsetsCD19+Mac-1+ Peripheral Blood
    CD4+CD4+CD44highCD8+CD8+CD44high
    Male BXSB→male BXSB TCRα−/−0.4 ± 0.050.4 ± 0.113.7 ± 0.5b83.0 ± 1.83.4 ± 0.371.4 ± 1.458.9 ± 1.225.1 ± 2.8
    Female BXSB→male BXSB TCRα−/−0.4 ± 0.10.3 ± 0.116.6 ± 0.784.6 ± 1.72.4 ± 0.469.3 ± 3.454.6 ± 2.218.5 ± 2.9
    WT male BXSB0.38 ± 0.10.45 ± 0.0516.8 ± 1.988.4 ± 4.02.7 ± 0.2284.2 ± 2.179.2 ± 2.4**23.7 ± 4.8

    • a Spleen and LN (axillary, inguinal, cervical, and mesenteric) weights (in grams) of 4-mo-old WT male BXSB and of 9-mo-old αβ+ T cell-deficient male BXSB recipients of WT male or female CD3+ LN T cells. Lymphoid subsets are in percentages of total splenocytes or PBMC (mean ± SEM of five to eight mice per group) and, in the case of CD44high cells, as percentages of CD4+ or CD8+ cells.

    • b , p < 0.05 between male BXSB→male BXSB TCRα−/− mice and either of the other groups.

    • c ∗, p < 0.05 between the WT male BXSB mice and either male TCRα−/− recipient groups.

  • Table IV.

    Kidney disease in αβ+ T cell-deficient male BXSB recipients of CD3+ T cells from WT BXSB male or female micea

    GNBlood Urea NitrogenImmune Complex Deposit Score
    Male BXSB→male BXSB TCRα−/−2.9 ± 0.23.0 ± 0.33.0 ± 0.2
    Female BXSB→male BXSB TCRα−/−3.0 ± 0.22.8 ± 0.22.8 ± 0.2
    WT male BXSB3.4 ± 0.23.0 ± 0.23.1 ± 0.3

    • a GN, blood urea nitrogen, and immune complex deposits of 4-mo-old WT male BXSB and of 9-mo-old αβ+ T cell-deficient male BXSB recipients of WT male or female CD3+ LN T cells (mean ± SEM of five to eight mice per group).

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