Background: The study of specific T-cell responses to vaccines against CSFV is important for understanding long-term immunity and infection management. The administration of a subunit vaccine against swine pathogens has been demonstrated to be safe and effective in infected pigs. However, subunit vaccines usually need an effective immunomodulatory adjuvant to stimulate active immune responses. Objectives: CD86 plays a crucial role in the immune response by enhancing the ability of APCs to stimulate the maturation and activation of T lymphocytes. Therefore, CD86 may act as a potential molecular adjuvant due to its ability to increase cytokine expression, which is protective against T-cell activation in pathogens. Methods: In this study, the CD86 coding sequence was linked with the CSFV E2 antigen sequence and then expressed in CHO cells for production of the fusion protein as an E2-CD86 vaccine. Commercial pigs aged 5–6 weeks were randomized into four groups: those inoculated with E2, E2-CD86, commercial Bayovac® CSF-E2 vaccines and the saline group. All animals were boosted 2 weeks after primary vaccination. Results: After vaccination, we evaluated the humoral response and compared it with that of T cells with the aim of correlating both types of responses and increasing CSFV-specific E2 antibody detection. The results revealed that the percentages of CD3+CD4+/CD8+, CD4+IL2+, IFNγ+ and CD4+CD8+ (DP) T cells among the PBMC 14 days after primary vaccination were significantly greater in the E2-CD86 group than in the other groups. The ELISpot results revealed a significant increase in the number of E2-specific IFNγ+ cells on D21 after vaccination. Conclusions: These results suggest that CD86 may enhance cellular immunity by increasing the levels of IL-2 and IFNγ-positive cells. Therefore, CD86 can act as a potential immuno-modulatory adjuvant in the development of subunit vaccines because of its protective efficacy.