Pertussis toxin activates adult and neonatal naive human CD4+ T lymphocytes

Abstract

Pertussis toxin (PTX) is known to be mitogenic for T lymphocytes, but its direct action on naive human T cells has not been specified. Herein, we show that PTX induces the proliferation of purified adult CD45RA+CD4+ T cells independently of its ADP-ribosyltransferase activity. PTX directly induces TNF-α and IL-2 mRNA expression, modulates the level of several cell surface receptors and induces Forkhead box p3 (Foxp3) protein accumulation in naive CD4+ T cells. Addition of autologous dendritic cells was found to be required for the production of high levels of IFN-γ by PTX-stimulated naive T cells. These effects of PTX occurred in conjunction with activation of NF-κB and NFAT transcription factors. Overall, responses of neonatal CD4+ T cells to PTX were similar to those of adult CD45RA+CD4+ naive T cells except for their blunted CD40 ligand up-regulation. We suggest that the adjuvant properties of PTX during primary cell-mediated immune responses involve a direct action on naive T lymphocytes in addition to activation of antigen-presenting cells. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.