The cytokine IL-21 is closely related to IL-2 and IL-15, a cytokine family that uses the common γ-chain for signaling. IL-21 is expressed by activated CD+ T cells. We examined the role of IL-21 in the autoimmune disease experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. IL-21 administration before induction of EAE with a neuroantigen, myelin oligodendrocyte glycoprotein peptide 35-55, and adjuvant enhanced the inflammatory influx into the CNS, as well as the severity of EAE. Autoreactive T cells purified from IL-21-treated mice transferred more severe EAE than did the control encephalitogenic T cells. No such effects were observed when IL-21 was administered after EAE progressed. Additional studies demonstrated that IL-21 given before the induction of EAE boosted NK cell function, including secretion of IFN-γ. Depletion of NK cells abrogated the effect of IL-21. Therefore, IL-21, by affecting NK cells, has differential effects during the initiation and progression of autoimmune responses against neuroantigens.
Differential effects of IL-21 during initiation and progression of autoimmunity against neuroantigen / Vollmer, T. L.; Liu, R.; Price, M.; Rhodes, S.; La Cava, A.; Shi, F. -D.. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 174:5(2005), pp. 2696-2701. [10.4049/jimmunol.174.5.2696]
Differential effects of IL-21 during initiation and progression of autoimmunity against neuroantigen
La Cava A.;
2005
Abstract
The cytokine IL-21 is closely related to IL-2 and IL-15, a cytokine family that uses the common γ-chain for signaling. IL-21 is expressed by activated CD+ T cells. We examined the role of IL-21 in the autoimmune disease experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. IL-21 administration before induction of EAE with a neuroantigen, myelin oligodendrocyte glycoprotein peptide 35-55, and adjuvant enhanced the inflammatory influx into the CNS, as well as the severity of EAE. Autoreactive T cells purified from IL-21-treated mice transferred more severe EAE than did the control encephalitogenic T cells. No such effects were observed when IL-21 was administered after EAE progressed. Additional studies demonstrated that IL-21 given before the induction of EAE boosted NK cell function, including secretion of IFN-γ. Depletion of NK cells abrogated the effect of IL-21. Therefore, IL-21, by affecting NK cells, has differential effects during the initiation and progression of autoimmune responses against neuroantigens.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.