T cells with high avidity for antigens are thought to mediate more effective immunity against foreign antigens and cause more severe autoimmunity. The impact of T cell receptor (TCR) avidity on the development of lupus has not been investigated. We took advantage of a transgenic mouse strain (designated MTB) that has a diverse T cell population and a globally stronger reactivity to self. [MTBxBXSB]F1 mice displayed accelerated lupus relative to the [WTxBXSB]F1 controls. The severity of lupus and the activation of T cells subsided with aging, when elevated IL-10 production by Tr1 cells was observed. Thus, chronic high avidity interactions of T cells with self-antigens can lead to an age associated increase in IL-10 production. This could explain the age-associated reduction of the incidence of lupus, as well as other autoimmune diseases. Furthermore, the principle of Tr1 differentiation based on diverse T cells with high avidity for self may potentially be used as a therapeutic strategy in the treatment of lupus. Lupus (2010) 19, 182—191.
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