Memory T lymphocytes of the immune system provide long-term protection in response to bacterial or viral infections/immunization. Ag concentration has also been postulated to be important in determining whether T cell differentiation favors effector versus memory cell development. In the present study we hypothesized that naïve Ag-specific CD4⁺ T cells briefly stimulated with different Ag doses at the primary exposure could affect establishment of memory cell pool after secondary immunization.

To assess this hypothesis, the response kinetics of DO11.10 TCR CD4+ T cells primed with different Ag doses in vitro was measured after adoptive transfer to naive BALB/c mice.

Maximum expansion was shown in cells primarily stimulated with high doses of ovalbumin peptide (OVA_323-339), whereas cells in vitro stimulated with low dose were expanded slightly after in vivo secondary exposure. However, the cells primed with low OVA_323-339 peptide dose showed least contraction and established higher number of memory cells than other treated groups. When the cell division was analyzed after adoptive transfer, the high dose Ag-stimulated donor cells have undergone seven rounds of cell division at 3 days post-adoptive transfer. However, there was very few division in naive and low dose of peptide-treated group.

These results suggest that primary stimulation with a low dose of Ag leads to better memory CD4⁺ T cell generation after secondary immunization. Therefore, these facts imply that optimally primed CD4⁺ T cells is necessary to support effective memory pool following administration of booster dose in prime-boost vaccination.