Pertussis toxin activates adult and neonatal naive human CD4+ T lymphocytes.
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-alpha 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-gamma by PTX-stimulated naive T cells. These effects of PTX occurred in conjunction with activation of NF-kappaB 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.
Tonon
Sandrine
S
Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium.
Badran
Bassam
B
Benghiat
Fleur Samantha
FS
Goriely
Stanislas
S
Flamand
Véronique
V
Willard-Gallo
Karen
K
Willems
Fabienne
F
Goldman
Michel
M
De Wit
Dominique
D
D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037342:Pertussis Toxin / Q000494:pharmacology*; D016192:Resting Phase, Cell Cycle / Q000276:immunology*
D037342:Pertussis Toxin