Tuftsin-derived T-peptide prevents cellular immunosuppression and improves survival rate in septic mice

The primary mechanisms of sepsis induced cellular immunesuppression involve immune dysfunction of T lymphocytes and negative immunoregulation of regulatory T cells (Tregs). It has been found that tuftsin is an immune modulating peptide derived from IgG in spleen. T-peptide is one of tuftsin analogs. Herein, we examined the effect of T-peptide on cell-mediated immunity in the presence of lipopolysaccharide (LPS) and the survival rate in septic mice. T-peptide regulated the proliferative ability of CD4(+)CD25(-) T cells in dual responses. Meanwhile, 10 and 100 mu g/ml T-peptides were able to enhance the apoptotic rate of CD4(+)CD25(+)T cells compared with 1 mu g/ml T-peptide, but markedly lowered interleukin (IL)-2 levels. When CD4(+)CD25(-) Tregs were treated with T-peptide for 24 hours, and co-cultured with normal CD4(+)CD25(-)T cells, the suppressive ability of CD4(+)CD25(+) Tregs on CD4(+)CD25(-)T cells was significantly lowered, along with decreased expression in forkhead/winged helix transcription factor p-3 (Foxp-3) as well as cytotoxic T lymphocyte-associated antigen (CTLA)-4, and secretion of transforming growth factor (TGF)-beta. Moreover, T-peptide has the ability to improve outcome of septic mice in a dose-and time-dependent manner, and associated with improvement in the microenvironment of cellular immunosuppression in septic mice.