Differential Impact of Chronic Hyperglycemia on Humoral Versus Cellular Primary Alloimmunity
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Figures
- Figure 1
No effect of chronic hyperglycemia on primary T-cell responses to alloantigen. A: PLN cell counts in alloimmunized mice. B: CD4+ and CD8+ cell counts in PLN. C: Frequency of responding Ki67+CD44hi cells in PLN. D: Geometric mean fluorescence intensity (gMFI) of IFNγ in Ki67+CD44hi cells. Black bars, B6; white bars, Akita. n = 6–8 per group from seven independent experiments. No significant differences after multiple Student t tests with Bonferroni-Dunn corrections.
- Figure 2
No effect of chronic hyperglycemia on responses of either direct or indirect alloreactive TCR transgenic adoptively transferred cells. A: Number of direct (4C) and indirect (TCR75) alloreactive T cells in draining PLNs of Akita mice and euglycemic littermates 5 days after local alloimmunization. B: Frequency of proliferating (Ki67+) direct (4C) and indirect (TCR75) cells. C: Geometric mean fluorescence intensity (gMFI) of IFNγ in direct (4C) and indirect (TCR75) cells. Black circles, B6; white squares, Akita. Number of samples with no detectable cells in unchallenged mice indicated adjacent to “n.d.” n = 4 per group from four independent experiments. No significant differences between immunized groups after multiple Student t tests with Bonferroni-Dunn corrections.
- Figure 3
No impact of chronic hyperglycemia on cellular responses to islet allografts. A: Survival curves of islet allograft acute rejection. n = 10–15. ***P < 0.001, Akita vs. SzB6; *P < 0.05, Akita vs. SzAkita; SzB6 vs. SzAkita not significant by nonparametric Mann-Whitney U test. B: Total numbers of graft-infiltrating cells at day 7. Numbers of CD4+ (C) and CD8+ T cells (D) within CD90+ graft-infiltrating cells. E: Frequency of responding Ki67+CD44hi cells within CD90+CD8+ graft-infiltrating cells. F: Geometric mean fluorescence intensity (gMFI) of IFNγ in CD90+CD8+FoxP3−Ki67+CD44hi T cells. G: Frequency of FoxP3+ cells within CD90+CD4+ graft-infiltrating cells. Ratio of CD90+CD4+FoxP3+ regulatory T cells to CD90+FoxP3−Ki67+CD44hi CD4+ (H) and CD8+ (I) effector T cells. Black circles, B6; white squares, Akita; black triangles, SzB6; white diamonds, SzAkita. In B–I, n = 4–6 per group from five independent experiments. Two-way ANOVA with Bonferroni corrections: **P < 0.01; ***P < 0.001; ****P < 0.0001.
- Figure 4
Impaired humoral response to alloantigen in chronic diabetes. H-2d–expressing A20 target cells were exposed to serum from alloimmunized mice (A and B, n = 9–16 per group from four independent experiments) or islet allograft recipients (C and D, n = 4–8 per group from two independent experiments). A: Geometric mean fluorescence intensity (gMFI) of anti-IgM. B: gMFI of anti-IgG. C: gMFI of anti-IgM. D: gMFI of anti-IgG. Multiple Student t tests with Bonferroni-Dunn corrections: *P < 0.05; **P < 0.01; ***P < 0.001. Pre-TP, pretransplant.
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