Neonatal impaired response to viral superantigen encoded by MMTV(SW) and Mtv-7.

Abstract

MMTV(SW) is an exogenous mouse mammary tumor virus that codes for a superantigen sharing the same V beta specificity as Mtv-7 (Mis-1a). Neonatal mice infected by suckling-infected milk show a deletion of the CD4+ V beta 6+ T cell subset within 8 weeks. In contrast, adult mice infected by injection of the virus in the footpad have a much faster deletion, which occurs within 2 weeks. In the present work, we investigated possible mechanisms for the different kinetics of deletion in the adult and newborn mice. To find out if the route of infection could be responsible for this discrepancy, we infected 5-day-old and adult mice by injection in the footpad. Our results demonstrate that the route of infection is not responsible for the delayed kinetics of reactive T cell deletion since newborn mice injected with the virus show similar kinetics to neonates infected by maternal milk. To exclude differences in viral spreading between the two models, we used a PCR assay to detect proviral DNA. Spreading of the virus was shown to occur at a similar rate or even more rapidly in neonates than in adults. We also compared the activation induced by MMTV(SW) or Mis-1a spleen cells in the draining lymph node in neonatal and adult mice and showed that a poor local activation is induced in neonates compared with adults. In vitro, neonatal T cell reactivity to anti-V beta 6 antibody was also impaired. Thus, the delay in clonal deletion could be linked to impaired expression, presentation and/or response to the viral superantigen. Our results suggest that the initial response to MMTV(SW) could be of importance for the kinetics of reactive T cell deletion.