Stimulation via CD40 can substitute for CD4 T cell function in preventing reactivation of a latent herpesvirus

Reactivation of latent herpesviruses is a particular problem in immunocompr omised individuals, such as AIDS patients, who lack effective CD4 T helper cell function. An important question is whether residual immune defenses ca n be mobilized to combat such opportunistic infections, in the absence of C D4 T cells. In the present study, we used a mouse model of opportunistic in fection to determine whether stimulation via CD40 could substitute for CD4 T cell function in preventing reactivation of a latent herpesvirus. Treatme nt with an agonistic antibody to CD40 was highly effective in preventing re activation of latent murine gammaherpesvirus (MHV-tis) in the lungs of CD4 T cell-deficient mice. CD8(+) T cells were essential for this effect, where as virus-specific serum antibody was undetectable and IFN-gamma production was unchanged. This demonstration that immunostimulation via CD40 can repla ce CD4 T cell help in controlling latent virus in vivo has potential implic ations for the development of novel therapeutic agents to prevent viral rea ctivation in immunocompromised patients.