CD4+ T cell priming accelerates the clearance of Sendai virus in mice, but was a negative effect on CD8+ T cell memory

Current vaccines designed to promote humoral immunity to respiratory virus infections also induce potent CD4(+) T cell memory. However, little is known about the impact of primed CD4(+) T cells on the immune response to heterologous viruses that are serologically distinct, but that share CD4+ T cell epitopes, In addition, the protective capacity of primed CD4(+) T cells has not been fully evaluated. In the present study, we addressed these two issues using a murine Sendai virus model, Mice were primed with an HN421-436 peptide that represents the dominant CD4(+) T cell epitope on the hemagglutinin-neuraminidase (HN) of Sendal virus. This vaccination strategy induced strong CD4(+) T cell memory to the peptide, but did not induce Abs specific for the Sendai virus virion. Subsequent Sendai virus infection of primed mice resulted in 1) a substantially accelerated virus-specific CD4(+) T cell response in the pneumonic lung; 2) enhanced primary antiviral Ah-forming cell response in the mediastinal lymph nodes; and 3) accelerated viral clearance. Interestingly, the virus-specific CD8(+) T cell response in the lung and the development of long-term memory CD8(+) T cells in the spleen were significantly reduced. Taken together, our data demonstrate that primed CD4(+) T cells, in the absence of pre-existing Ab, can have a significant effect on the subsequent immune responses to a respiratory virus infection.