Adoptive transfer of cytomegalovirus-specific effector CD4+ T cells provides antiviral protection from murine CMV infection.
Cytomegalovirus (CMV) infects a majority of the human population and establishes a life-long persistence. CMV infection is usually asymptomatic but the virus carries pathogenic potential and causes severe disease in immunocompromised individuals. T-cell-mediated immunity plays an essential role in control of CMV infection and adoptive transfer of CMV-specific CD8(+) T cells restores viral immunity in immunosuppressed patients but a role for CD4(+) T cells remains elusive. Here, we analyzed in adoptive transfer studies the features and antiviral functions of virus-specific CD4(+) T cells during primary murine CMV (MCMV) infection. MCMV-specific CD4(+) T cells expanded upon MCMV infection and displayed an effector phenotype and function. Adoptive transfer of in vivo activated MCMV-specific CD4(+) T cells to immune-compromised mice was protective during pathogenic MCMV infection and IFN-γ was a crucial mediator of this protective capacity. Moreover, co-transfer of low doses of both MCMV-specific CD4(+) T cells and CD8(+) T cells synergized in control of lytic viral replication in immune-compromised mice. Our data reveal a pivotal antiviral role for virus-specific CD4(+) T cells in protection from pathogenic CMV infection and provide evidence for their antiviral therapeutic potential.
Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
Sanja Mandaric
SM
Jeitziner
Senta M
SM
Walton
Nicole
N
Torti
Annette
A
Oxenius
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000517:prevention & control; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014779:Virus Replication / Q000276:immunology
D007371:Interferon-gamma
Adoptive immunotherapy; CD4+ T cells; Cytomegalovirus infection