Society of Toxicologic Pathology Student Speaker Award

Angela Brice, DVM, Johns Hopkins University

MINOCYCLINE ARRESTS CD4+ T CELLS IN THE G0/G1 PHASE OF THE CELL CYCLE AND INCREASES THE ACTIVATION THRESHHOLD. A. K. Brice, D. R. Graham, M. C. Zink. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD.
   Proteins such as cMyc, cyclin D1, CDK4 and pRb are essential for progression through the G0/G1 and S phases of the cell cycle. Minocycline, a semisynthetic tetracycline derivative, decreases CD4+ T cell proliferation and IL2 responsiveness. The mechanism for this immunosuppression has not been clearly elucidated. We demonstrated that minocycline-treated CD4+ T cells were arrested in the G0/G1 phase and had significantly lower expression of proteins necessary for G0/G1 phase progression including cMyc, cyclin D1, CDK4 and pRb. We further showed that minocycline-treated CD4+ T cells had significantly lower surface CD25 expression following stimulation by anti-CD3 and anti-CD28 antibodies as compared to untreated controls. High levels of exogenous IL-2 followed by higher concentrations of stimulating antibodies significantly increased surface CD25 expression in treated cultures. These data suggest that minocycline targets the G0/G1 phase of the cell cycle through the reduced expression of key cell cycle regulators and that minocycline-treated T cells have a heightened threshold for activation. Since HIV relies on host cell cycle progression for its life cycle, this may explain our and others finding that minocycline suppresses HIV replication.