CD4+ T cells are required for lethal disease in LCMV-infected STAT1 KO mice. (A) Compared with Ig-treated controls (left), mice administered neutralizing monoclonal antibodies against CD8 (middle) or CD4 (right) showed less than 0.5% remaining CD8+ and CD4+ cells, respectively. Depletion of CD4+ T cells had no impact on the survival of WT mice infected i.p. or i.c. with LCMV (B and D) but prevented lethal disease in STAT1 KO mice independent of the route of infection (C and E). In contrast, depletion of CD8+ T cells rescued WT mice infected i.c. with LCMV (D) but did not alter the clinical course of WT mice infected i.p (B) or of STAT1 KO mice infected i.c. (E) with LCMV. (C) Depletion of CD8+ T cells significantly (**, P < 0.05) increased the survival time of STAT1 KO mice infected i.p. with LCMV but did not prevent lethal disease. Prominent mononuclear infiltrates and tissue destruction were evident in the livers (F), kidneys (G), and lungs (H) of STAT1 KO mice infected i.p. with LCMV. In contrast, in similarly infected STAT1 KO mice that were depleted of CD4+ T cells, the livers (I), kidneys (J), and lungs (K) showed only minor mononuclear infiltrates and no obvious organ destruction.