The Kinetics of Secondary Response of Antigen-Specific CD4+ T Cells Primed in vitro with Antigen

ABSTRACT

BACKGROUND: 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 na?ve 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. METHODS: 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. RESULTS: Maximum expansion was shown in cells primarily stimulated with high doses of ovalbumin peptide (OVA323-339), whereas cells in vitro stimulated with low dose were expanded slightly after in vivo secondary exposure. However, the cells primed with low OVA323-339 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. CONCLUSION: 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.