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 immunocompromised individuals, such as AIDS patients, who lack effective CD4 T helper cell function. An important question is whether residual immune defenses can be mobilized to combat such opportunistic infections, in the absence of CD4 T cells. In the present study, we used a mouse model of opportunistic infection to determine whether stimulation via CD40 could substitute for CD4 T cell function in preventing reactivation of a latent herpesvirus. Treatment with an agonistic antibody to CD40 was highly effective in preventing reactivation of latent murine gammaherpesvirus (MHV-68) in the lungs of CD4 T cell-deficient mice. CD8(+) T cells were essential for this effect, whereas virus-specific serum antibody was undetectable and IFN-gamma production was unchanged. This demonstration that immunostimulation via CD40 can replace CD4 T cell help in controlling latent virus in vivo has potential implications for the development of novel therapeutic agents to prevent viral reactivation in immunocompromised patients.
Sarawar
S R
SR
Divisions of Molecular Immunology and Immune Regulation, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA. ssarawar@liai.org
Lee
B J
BJ
Reiter
S K
SK
Schoenberger
S P
SP
D016475:3T3 Cells; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D018142:Gammaherpesvirinae / Q000254:growth & development / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014775:Virus Activation / Q000276:immunology*; D017735:Virus Latency / Q000276:immunology*
D000914:Antibodies, Viral; D019013:CD40 Antigens; D007371:Interferon-gamma