Profiling pharmacokinetics of double-negative T cells and cytokines via a single intravenous administration in NSG mice

Abstract

This study was intended to delineate the profile of double-negative T cells (DNTs) in NOD.Cg-Prkdc^scid Il2rg^tm1wj /SzJ mice and cytokines released from DNTs in vivo and in vitro. Total 4 × 10⁷ cells of RC1012 injection per mice were intravenously infused. IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10 were measured in vivo and in vitro. A quantitative polymerase chain reaction (PCR) was employed to determine the gene copies of Notch2-NLA per DNT cell from collected organs. Cytokines were significantly increased in vitro (4 h) and in vivo (3 h). DNT cells were distributed into the lung, liver, heart, and kidney earlier, and redistributed to lymphocyte homing spleen and bone marrow, which seemed to frame a two-compartment pharmacokinetics (PK) model but more data are needed to confirm this, and the clearance of DNT cells fell into first-order kinetics.

Keywords: cytokine; double negative T cell; pharmacodynamics; pharmacokinetics.