Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells
J. Clin. Invest. Hélène Bour-Jordan, et al. 114:979 doi:10.1172/JCI20483 [Go to this article.]

Figure 4
Treg’s suppress autoreactive T cell activation in NOD_B7-2^_/_ mice. NOD_B7-2^_/_ recipients were thymectomized to avoid rapid repopulation of the peripheral Treg compartment by CD4⁺CD25⁺ Treg’s emigrating from the thymus (46) and then treated with anti-CD25 mAb’s to deplete Treg’s. Moreover, the adoptive transfer of purified naive BDC2.5 T cells was delayed 2 weeks after anti-CD25 treatment to allow the antibody to clear from the circulation. (A) NOD mice were treated with control Ig (left) and NOD_B7-2^_/_ mice were treated with control Ig (middle) or anti-CD25 mAb’s (PC61) (right). Transfer of BDC2.5 cells and analysis in the pancreatic LNs was as described in Figure 1A. A representative experiment is shown. (B) The results of 3 separate experiments performed as described in A are shown. Percentage of cycled CFSE⁺ cells in the pancreatic LNs was calculated as in Figure 1B in NOD, NOD_B7-2^_/_, and NOD_B7-2^_/_ depleted of Treg’s. Each histogram represents the mean and standard deviation of each group. The P value for the t test between the relevant groups is shown. The same result was obtained when comparing geometric means instead of means (t test, P < 0.05). (C) We depleted Treg’s from NOD or NOD_B7-2^_/_ spleen cells using anti-CD25 mAb’s (7D4) and rabbit complement. We transferred total spleen cells from NOD_B7-2^_/_ mice (filled squares; n = 5) or CD25-depleted spleen cells from NOD mice (open triangles; n = 4) or NOD_B7-2^_/_ mice (filled circles; n = 9) into NOD-SCID recipients. We followed blood glucose levels weekly after transfer to assess the development of diabetes.