Pertussis toxin reduces the number of splenic Foxp3+ regulatory T cells.
Pertussis toxin (PTx) is a bacterial toxin used to enhance the severity of experimental autoimmune diseases such as experimental autoimmune encephalomyelitis. It is known to promote permeabilization of the blood-brain barrier, maturation of APC, activation of autoreactive lymphocytes and alteration of lymphocyte migration. In this study, we show that i.v. injection of PTx in mice induces a decrease in the number of splenic CD4(+)CD25(+) regulatory T cells (Treg cells). Furthermore, PTx not only induces a depletion of the dominant CD4(+)CD25(+)Foxp3(+) subpopulation of splenic Treg cells, but also reduces to a similar extent the CD4(+)CD25(-)Foxp3(+) subpopulation. On a per cell basis, the suppressive properties of the remaining Treg cells are not modified by PTx treatment. The reduction in splenic Treg cells is associated with preferential migration of these cells to the liver. Additionally, Treg cells exhibit a high sensitivity to PTx-mediated apoptosis in vitro. Finally, in vivo depletion of Treg cells by injection of an anti-CD25 Ab, and PTx treatment, present synergistic experimental autoimmune encephalomyelitis exacerbating effects. Therefore, we identify a new effect of PTx and provide an additional illustration of the influence of microbial components on the immune system affecting the balance between tolerance, inflammation and autoimmunity.
Cassan
Cécile
C
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Piaggio
Eliane
E
Zappulla
Jacques P
JP
Mars
Lennart T
LT
Couturier
Nicolas
N
Bucciarelli
Florence
F
Desbois
Sabine
S
Bauer
Jan
J
Gonzalez-Dunia
Daniel
D
Liblau
Roland S
RS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006131:Growth Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D037342:Pertussis Toxin / Q000008:administration & dosage* / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D037342:Pertussis Toxin