Depleting anti-CD4 monoclonal antibody (GK1.5) treatment:: Influence on regulatory CD4+CD25+Foxp3+ T cells in mice

Background. CD4(+)CD25(+) regulatory T (Treg) cells are often essential for the maintenance of immunologic self-tolerance and transplant tolerance in some cases. The effects of depleting anti-CD4 monoclonal antibody (GK1.5), which was used in transplant tolerance induction, on CD4(+)CD25(+) Treg cells have not been investigated. Methods. Three weeks after BALB/c mice were injected with GK1.5 or phosphate-buffered saline, the levels, phenotype and immunosuppressive function of CD4(+)CD25(+) Treg cells in these mice were detected. Results. The numbers of CD4(+) and CD4(+)CD25(+) Treg cells in the periphery were markedly decreased in GK1.5-treated mice. However, GK1.5 treatment significantly enhanced the ratios of CD4+CD25+ T cells or CD4(+)CD25(+)FoXP3(+) T cells to CD4+ T cells in the periphery (P < 0.01). Compared with the control mice, more CD4+CD25+ T cells in GK1.5-treated mice showed CD45RB(low) and CD62L(low) phenotype. Furthermore, enriched CD4(+)CD25(+) Treg cells in GK1.5-treated mice show immunosuppressive ability on the immune response of T effector cells to alloantigens or mitogen as efficiently as those from the control mice in vitro. Conclusions. GK1.5 could significantly enhance the percentage of CD4(+)CD25(+)Foxp3(+) Treg cells in the periphery while keeping these cells functional, indicating that GK1.5 might affect the potential induction of immune tolerance by different influences on CD4(+)CD25(+) Treg cells and CD4(+)CD25(-) T cells in periphery.