IL-21R–deficient mice exhibit a Th1 R^−/− response following infection with Leishmania major and Th 17-mediated protection from autoimmune myocarditis. (A,B) C57BL/6 and IL-21 (N5, C57BL/6) were infected with 2 × 10⁶ promastigotes of L major in the hind footpad. (A) At the time points indicated, the course of disease was monitored using metric calipers to determine footpad swelling. (B) Three weeks after infection, the draining lymph node was removed and isolated cells were restimulated with PMA and ionomycin for 4 hours. IFN-γ production by CD4⁺ T cells was assessed by FACS. Values show percentage of IFN-γ–producing cells, gated on CD4⁺ cells. Data are from a representative experiment using 3 to 5 mice per group. (C,D) IL-21R^−/− (N4, BALB/c) and littermate control IL-21R^+/− mice were immunized with α-myosin-peptide in CFA on days 0 and 7, and were killed 14 days later. Hearts were removed and fixed in 4% buffered formalin, and histological sections were evaluated. (C) The severity of inflammatory infiltrates were assessed and scored as described in “Materials and methods.” Horizontal lines represent the median value for each group. (D) Representative images of H&E-stained heart tissue. Original magnification, 15× (left column), 60× (middle column), and 400× (right column).