Expression Time and Peak Concentration Dendritic Cells, Perforin, and Granzyme B in Invivo and Invitro Studies: A Systematic Review

Abstract

Dendritic cells, perforin, and granzyme B are pivotal in immune regulation, yet the timing of their expression and peak concentration remains variably reported across studies. This systematic review aimed to summarize and compare the expression time and peak concentration of dendritic cells, perforin, and granzyme B from in vivo and in vitro studies. A systematic search was conducted in PubMed, ScienceDirect, ResearchGate, and Google Scholar for studies published between 1990 and 2024. Eligible studies included experimental in vitro, in vivo, or clinical investigations reporting temporal expression or peak concentration of DCs, perforin, or granzymes. Data were extracted on study design, methods, and outcomes, and risk of bias was assessed using SYRCLE’s and Cochrane tools. From 732 identified records, 11 studies met inclusion criteria. In vitro studies consistently demonstrated that DCs reached optimal antigen-presenting function on day 7, with immature DCs (day 5) showing stronger antigen uptake. Perforin expression was detected early, peaking around days 2–4 across murine CD8⁺ T cell activation, influenza infection, uterine implantation, and kidney transplant rejection. Granzyme B followed a similar rapid induction, rising at days 2–3 and peaking at days 3–4, sustaining cytotoxic T cell activity. In contrast, granzyme A and C appeared later (days 5–7), providing complementary effector functions. Translational studies demonstrated the biomarker potential of these molecules: perforin mRNA peaked at the onset of acute rejection, while granzyme B expression and PET imaging distinguished responders from non-responders to immunotherapy. Dendritic cell maturation, perforin, and granzymes display distinct yet coordinated temporal dynamics. DCs optimize antigen presentation by day 7, perforin and granzyme B mediate rapid early cytotoxic responses, and granzyme A/C contribute to later effector phases. These findings provide mechanistic insight into immune regulation and support the clinical utility of perforin and granzyme B as biomarkers of immune activation and therapeutic response.