Neonates develop heterologous immunity but with altered crossreactivities (P6151)

Abstract

Abstract The neonatal immune system is immature, lacks memory and is undergoing tolerization. This is also the age when children receive multiple vaccines. Previously, we have shown that sequential infection with unrelated pathogens can alter disease outcome. This is defined as heterologous immunity and is mediated by crossreactive T cells. In adult mice previous exposure to LCMV protects mice from lethal vaccinia virus (VV) infection. Crossreactive LCMV-specific memory cells recognize VV epitopes, are reactivated and expand during VV infection. This causes faster viral clearance and a skewing of the LCMV-specific immunodominance hierarchy. However, some LCMV-immune mice also develop acute fatty necrosis (AFN) of the abdominal fat pads during a VV infection. We questioned if mice immunized as neonates would have protective heterologous immunity during VV challenge. Mice immunized as neonates had comparable reduction in VV load and induction of AFN indicating that heterologous immunity is established during viral infections early in life. Interestingly, the LCMV-specific memory populations that expanded in mice immunized as neonates differed from that of mice immunized as adults. In adult mice 50% of the mice have an expansion of LCMV-NP205-specific CD8 T cells while the majority of neonates expanded the LCMV-GP34-specific CD8 T cell pool. This alteration in dominant crossreactivities may be due to the limited T cell receptor repertoire of neonatal mice.