CD4 T-cell-independent antibody response reduces enterovirus 71 lethality in mice by decreasing tissue viral loads

Enterovirus 71 (EV71) has induced fatal encephalitis in hundreds of thousands of infants and young children in the Asia-Pacific region since the past decade. Lymphocyte and antibody responses have been suspected to aggravate EV71-induced neurological symptoms, so anti-inflammatory agents have been used to treat patients with neurological symptoms. In the present study, we found that mice deficient in CD4(+) T cells were resistant to EV71 infection as wild-type mice, whereas mice deficient in B cells were highly susceptible to viral infection. Compensation of CD4 T-cell function by other immune cells was not likely, because wild-type mice depleted of CD4(+) T cells were also resistant to viral infection. Infected CD4 T-cell-deficient mice produced virus-specific neutralizing antibodies, IgM and IgG. Moreover, adoptive transfer of the virus-specific antibody produced by infected CD4 T-cell-deficient mice protected B-cell-deficient mice from infection by reducing tissue viral loads. Collectively, our results show that the CD4 T-cell-independent antibody response promotes the survival of EV71-infected mice and suggest great potential for the use of vaccines and neutralizing antibodies to reduce fatal symptoms in patients.