Induction of Autoimmunity by Expansion of Autoreactive CD4 super(+)CD62L super(low) Cells In Vivo

• Published in: Journal of Immunology 2006-10, Vol.177 (7), p.4384-4390
• Main Authors: Amend, Bastian, Doster, Hong, Lange, Christian, Dubois, Evelyn, Kalbacher, Hubert, Melms, Arthur, Bischof, Felix
• Format: Article
• Language: English
• ISSN: 0022-1767; 1365-2567

The prerequisites of peripheral activation of self-specific CD4 super(+) T cells that determine the development of autoimmunity are incompletely understood. SJL mice immunized with myelin proteolipid protein (PLP) 139-151 developed experimental autoimmune encephalomyelitis (EAE) when pertussis toxin (PT) was injected at the time of immunization but not when injected 6 days later, indicating that PT-induced alterations of the peripheral immune response lead to the development of autoimmunity. Further analysis using IA super(s)/PLP sub(139-151) tetramers revealed that PT did not change effector T cell activation or regulatory T cell numbers but enhanced IFN- gamma production by self-specific CD4 super(+) T cells. In addition, PT promoted the generation of CD4 super(+)CD62L super(low) effector T cells in vivo. Upon adoptive transfer, these cells were more potent than CD4 super(+)CD62L super(high) cells in inducing autoimmunity in recipient mice. The generation of this population was paralleled by higher expression of the costimulatory molecules CD80, CD86, and B7-DC, but not B7-RP, PD-1, and B7-H1 on CD11c super(+)CD4 super(+) dendritic cells whereas CD11c super(+)CD8 alpha super(+) dendritic cells were not altered. Collectively, these data demonstrate the induction of autoimmunity by specific in vivo expansion of CD4 super(+)CD62L super(low) cells and indicate that CD4 super(+)CD62L super(low) effector T cells and CD11c super(+)CD4 super(+) dendritic cells may be attractive targets for immune interventions to treat autoimmune diseases.