| First Author | Tregoning JS | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 14 | Pages | 5576-81 |
| PubMed ID | 23509276 | Mgi Jnum | J:194232 |
| Mgi Id | MGI:5471849 | Doi | 10.1073/pnas.1214247110 |
| Citation | Tregoning JS, et al. (2013) Neonatal antibody responses are attenuated by interferon-gamma produced by NK and T cells during RSV infection. Proc Natl Acad Sci U S A 110(14):5576-81 |
| abstractText | Respiratory syncytial virus (RSV) infects most children in the first year of life and is a major single cause of hospitalization in infants and young children. There is no effective vaccine, and antibody generated by primary neonatal infection is poorly protective against reinfection even with antigenically homologous viral strains. Studying the immunological basis of these observations in neonatal mice, we found that antibody responses to infection were low and unaffected by CD4 depletion, in contrast with adult mice, which had stronger CD4-dependent antibody responses. Natural killer cell depletion or codepletion of CD4(+) and CD8(+) cells during neonatal RSV infection caused a striking increase in anti-RSV antibody titer. These cells are major sources of the cytokine IFN-gamma, and blocking IFN-gamma also enhanced RSV-specific antibody responses in neonates. In addition, infection with a recombinant RSV engineered to produce IFN-gamma reduced antibody titer, confirming that IFN-gamma plays a pivotal role in inhibition of antibody responses after neonatal infection. These unexpected findings show that the induction of a strong cellular immune response may limit antibody responses in early life and that vaccines that induce IFN-gamma-secreting cells might, in some situations, be less protective than those that do not. |
