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. 2011 Dec 12;61(1):155–165. doi: 10.2337/db11-0684

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© 2012 by the American Diabetes Association.

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FIG. 5. — Th1 to Th2 skewing of the immune response in the three immune settings of islet transplantation (allo, auto, and allo/auto) after B-cell depletion. Serum samples (n = 3 samples/experiment) and splenocytes (n = 3 mice/experiment) were analyzed in the three groups of islet-transplanted mice at day 14 in the BALB/c into C57BL/6 and NOD.SCID into NOD groups and at day 7 in the BALB/c into NOD group. Peripheral cytokine profiles and polarization of the auto- and alloimmune response were examined. 1) In allo, a decrease in the Th1 cytokine IFN-γ (*P < 0.05) and an increase in the Th2-relevant cytokines IL-4 (*P < 0.01) and IL-10 (*P < 0.001) were evident in B-cell–depleted mice compared with cal-treated and untreated mice (A1). These data were confirmed by the ELISpot assay in which donor-derived antigens (irradiated BALB/c splenocytes) were plated with splenocytes harvested from transplant recipients undergoing the different treatments. We found that anti-CD22/cal–treated mice exhibit a reduced number of IFN-γ–secreting cells compared with cal-treated and untreated mice (*P < 0.05) (A2), whereas IL-4–secreting cell numbers were significantly increased (*P < 0.05) (A3). 2) In auto, no change in peripheral cytokine levels was evident in the three groups of mice studied (B1), and similar numbers of IFN-γ– and IL-4–producing cells (B2 and B3, respectively) were observed after ex vivo restimulation with β-cell peptides (BDC2.5 and IGRP). 3) In allo/auto, examination of the cytokine profile (C1) revealed a systemic suppression of the inflammatory response (IL-6, *P < 0.01) with increased levels of the Th2-relevant cytokines IL-4 (*P < 0.01) and IL-10 (*P < 0.05) and a complete suppression in the Th1 immune response (IFN-γ, *P < 0.01; IL-2, *P < 0.01). In this animal model, both the allo- and autoimmune responses were examined (C2–5). Donor-derived antigen (BALB/c splenocytes) and islet peptides (BDC2.5 and IGRP) were plated with splenocytes harvested from the three groups of mice studied at day 7 after transplantation. B-cell–depleted mice displayed reduced numbers of IFN-γ–producing cells (*P < 0.05) and increased numbers of IL-4–producing cells (*P < 0.05) among both donor-specific T cells (stimulated using BALB/c splenocytes) (C2 and 4) and CD4⁺ (BDC2.5-stimulated, *P < 0.05) and CD8⁺ (IGRP-stimulated, *P < 0.05) (C3 and 5) autoreactive T cells.