CD40L treatment stimulated IgG2a production and improved survival of GVHD mice following HSV-1 infection but did not affect survival of B-cell–deficient mice. CD40L was given intraperitoneally (6 μg/mouse, three times a week) to control and GVHD mice. Vehicle-treated control and GVHD mice received glycerol diluted with saline. (A) Mice were inoculated with HSV-1 2 weeks before sacrifice. Serum was obtained by orbital bleed on day 14 immediately before killing. Total serum IgG2a was measured by radial immunodiffusion: (□) pre–HSV-1 infection, (▧) post–HSV-1 glycerol-treated, (▪) post–HSV-1 CD40L-treated. Significant differences (P < .05,t-test) were found between the glycerol and CD40L-treated GVHD groups. (B) Serum levels of HSV-1–specific and IgG2a were determined by ELISA 2 weeks post–HSV-1 infection: (▧) post–HSV-1 glycerol-treated, (▪) post–HSV-1 CD40L-treated. The increase in HSV-1–specific IgG2a in GVHD mice does not reach statistical significance. The data shown are the mean and SEM of six similar experiments that included 50 mice. (C) Mice were monitored daily for survival after infection with HSV-1. The GVHD-CD40L and GVHD-glycerol group are significantly different (P < .05, log-rank test). Each group included 15 mice. (D) Two groups of Igh-6 (B-cell–deficient) mice were inoculated with HSV-1 (1 × 10⁸ pfu, 4.5LD₅₀) and treated with: (□) CD40L or (▪) glycerol. Both groups of mice have similar survival. The CD40L and glycerol groups each included three mice.