Natural CD4 CD25(+) regulatory T cells control the burst of superantigen-induced cytokine production: the role of IL-10.
In normal mice a subpopulation of CD4 T cells constitutively expresses the IL-2 receptor alpha chain (CD25). This natural CD4 CD25(+) subset is thymus-born, constitutively expresses IL-10 mRNA,does not produce IL-2 and is resistant to apoptosis. These cells behave as regulatory T cells in the control of self-tolerance, inflammatory reactions and T cell homeostasis. The mechanisms by which natural CD4 CD25(+) cells control the immune response is unclear. We examined CD25-deficient mice, which over-express various cytokines, including proinflammatory molecules, after bacterial superantigen stimulation in vivo. We observed that this abnormal cytokine production could be controlled by the injection of natural CD4 CD25(+) T cells and that IL-10 production is needed, as CD4 CD25(+) T cells from IL-10 knockout mice do not correct cytokine over-production in vivo. As the circulating IL-10 produced by CD25-deficient mice was ineffective, we deduced that the key source of IL-10 was the regulatory T cell population. IL-10 is also involved in the control of cytokine production by normal T cells. However, the target of IL-10 in this control is undefined. Whether it acts directly on the effector T cells or on the regulatory CD4 CD25(+) T cells themselves to induce their functional maturation has to be clarified.
Pontoux
Christiane
C
INSERM U345, Institut Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Banz
Alice
A
Papiernik
Martine
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000502:physiology*; D053645:Interleukin-2 Receptor alpha Subunit; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D018089:Superantigens / Q000276:immunology*
D016207:Cytokines; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin; D015375:Receptors, Interleukin-2; D018089:Superantigens; D016753:Interleukin-10