Neonatal immunity develops in a transgenic TCR transfer model and reveals a requirement for elevated cell input to achieve organ-specific responses

In recent years, it has become clear that neonatal exposure to Ag induces r ather than ablates T cell immunity. Moreover, rechallenge with the Ag at ad ult age can trigger secondary responses that are distinct in the lymph node vs the spleen. The question addressed in this report is whether organ-spec ific secondary responses occur as a result of the diversity of the T cell r epertoire or could they arise with homogeneous TCR-transgenic T cells. To t est this premise, we used the OVA-specific DO11.10 TCR-transgenic T cells a nd established a neonatal T cell transfer system suitable for these investi gations. In this system, neonatal T cells transferred from I-day-old DO11.1 0/SCID mice into newborn (1-day-old) BALB/c mice migrate to the host's sple en and maintain stable frequency. The newborn BALB/c hosts were then given Ig-OVA, an Ig molecule carrying the OVA peptide, and challenged with the OV A peptide in CFA at the age of 7 wk; then their secondary responses were an alyzed. The findings show that the lymph node T cells were deviated and pro duced IL-4 instead of IFN-gamma and the splenic T cells, although unable to proliferate or produce IFN-gamma, secreted a significant level of IL-2. Su pply of exogenous IL-12 during Ag stimulation restores both proliferation a nd IFN-gamma production by the splenic T cells. This restorable form of spl enic unresponsiveness referred to as IFN-gamma -dependent anergy required a transfer of a high number of neonatal DO11.10/SCID T cells to develop. Thu s, the frequency of neonatal T cell precursors rather than repertoire diver sity exerts control on the development of organ-specific neonatal immunity.