Serum Antibodies Critically Affect Virus-Specific CD4+/CD8+ T Cell Balance during Respiratory Syncytial Virus Infections

Following infection with respiratory syncytial virus (RSV), reinfection in healthy individuals is common and presumably due to ineffective memory T cell responses. In peripheral blood of healthy adults, a higher CD4 + /CD8 + memory T cell ratio was observed compared with the ratio of virus-specific effector CD4 + /CD8 + T cells that we had found in earlier work during primary RSV infections. In mice, we show that an enhanced ratio of RSV-specific neutralizing to nonneutralizing Abs profoundly enhanced the CD4 + T cell response during RSV infection. Moreover, FcγRs and complement factor C1q contributed to this Ab-mediated enhancement. Therefore, the increase in CD4 + memory T cell response likely occurs through enhanced endosomal Ag processing dependent on FcγRs. The resulting shift in memory T cell response was likely amplified by suppressed T cell proliferation caused by RSV infection of APCs, a route important for Ag presentation via MHC class I molecules leading to CD8 + T cell activation. Decreasing memory CD8 + T cell numbers could explain the inadequate immunity during repeated RSV infections. Understanding this interplay of Ab-mediated CD4 + memory T cell response enhancement and infection mediated CD8 + memory T cell suppression is likely critical for development of effective RSV vaccines.