Differential effect of CD4+Foxp3+ T-regulatory cells on the B and T helper cell responses to influenza virus vaccination.

The T-regulatory (T-reg) cells restrict the T-cell functions in various viral infections including influenza infection. However little is known about the effect of T-regs in influenza vaccination. Herein, we found that immunization of BALB/c mice with a prototype of UV-inactivated influenza PR8/A/34 virus vaccine expanded the CD4(+)Foxp3(+) T-reg pool and fostered the development of virus-specific CD4(+)Foxp3(+) T-reg cells. Increasing the size of Foxp3(+) T-reg pool did not alter the primary PR8-specific B-cell response, but it did suppress the primary and memory PR8-specific T helper responses induced by vaccination. In contrast, the vaccination-induced T helper cell response was augmented in the absence of CD4(+)Foxp3(+) T-reg cells. Since CD4 T helper cells contribute to anti-influenza protection, therapeutic "quenching" of T-reg function prior to vaccination may enhance the efficacy of influenza vaccination.