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

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.

CD8+ T Cell-mediated Immunity Induced by Heterologous Prime-boost Vaccination Based on DNA Vaccine and Recombinant Vaccinia Virus Expressing Epitope

BACKGROUND: DNA vaccination represents an anticipated approach for the control of numerous infectious diseases. Used alone, however, DNA vaccine is weak immunogen inferior to viral vectors. In recent, heterologous prime-boost vaccination leads DNA vaccines to practical reality. METHODS: We assessed prime-boost immunization strategies with a DNA vaccine (minigene, gB498-505 DNA) and recombinant vaccinia virus (vvgB498- 505) expressing epitope gB498-505 (SSIEFARL) of CD8+ T cells specific for glycoprotein B (gB) of herpes simplex virus (HSV). Animals were immunized primarily with gB498-505 epitope-expressing DNA vaccine/recombinant vaccinia virus and boosted with alternative vaccine type expressing entire Ag. RESULTS: In prime-boost protocols using vvgBw (recombinant vaccinia virus expressing entire Ag) and vvgB498-505, CD8+ T cell-mediated immunity was induced maximally at both acute and memory stages if primed with vvgBw and boosted with vvgB498-505 as evaluated by CTL activity, intracellular IFN-staining, and MHC class I tetramer staining. Similarly gB498-505 DNA prime-gBw DNA (DNA vaccine expressing entire Ag) boost immunization elicited the strongest CD8+ T cell responses in protocols based on DNA vaccine. However, the level of CD8+ T cell-mediated immunity induced with prime-boost vaccination using DNA vaccine expressing epitope or entire Ag was inferior to those based on vvgBw and vvgB498-505. Of particular interest CD8+ T cell-mediated immunity was optimally induced when vvgB498-505 was used to prime and gB DNA was used as alternative boost. Especially CD8+ T cell responses induced by such protocol was longer lasted than other protocols. CONCLUSION: These facts direct to search for the effective strategy to induce optimal CD8+ T cell-mediated immunity against cancer and viral infection.