Paradoxical arrest in lupus activity in BXSB mice with highly autoreactive T cells.
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.
Stojakovic
M
M
Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010-2970, USA.
Tatari-Calderone
Z
Z
Maric
C
C
Hoang
A
A
Vukmanovic
S
S
D000367:Age Factors; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D002454:Cell Differentiation; D016753:Interleukin-10 / Q000096:biosynthesis*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10