Regulatory CD4+ T Cells Promote B Cell Anergy in Murine Lupus

Abstract

To prevent autoimmunity, anergy of autoreactive B cells needs to be maintained, together with the suppression of hyperactive B cells. We previously reported that CD4+CD25+Foxp3+ regulatory T cells (Tregs) can directly suppress autoantibody-producing autoreactive B cells in systemic lupus erythematosus. In this article, we show that Tregs can also reduce the production of autoantibodies in (NZB × NZW)F1 mouse lupus B cells by promoting B cell anergy, both in vitro and in vivo. This phenomenon associated with a reduction in Ca2+ flux in B cells, and CTLA-4 blockade inhibited the effects of Tregs on anergic lupus B cells. These findings identify a new mechanism by which Tregs can control production of autoantibodies in lupus B cells and, more generally, B cell activity in physiopathological conditions.

Regulatory T cells in kidney disease and transplantation

“…110,[118][119][120] In murine lupus Tregs have impaired suppression, altered homing, but when given therapeutically are protective and can prolong drug-induced remission. [121][122][123][124][125] In the rat model of spontaneous nephrotic syndrome, Tregs have also been shown to be protective. 126 In a nephrocalcinosis model of DBA/2 mice, depletion of Tregs using an anti-CD25 monoclonal antibody leads to worse acute phosphate nephropathy and worse mortality.…”

Serafino Zappacosta: An Enlightened Mentor and Educator

“…After training with Serafino Zappacosta with a focus on the immune-modulating properties of MHC molecules, the team members subsequently developed new hypotheses and investigations in diverse directions, ranging from the study of the fundamental mechanisms of immune regulation and immunological memory, to autoimmunity, cancer immunotherapy and vaccinology (58)(59)(60)(61)(62)(63)(64)(65)(66). Serafino Zappacosta kept to enthusiastically follow the progress of the past members of his team after they left to start their independent careers.…”

Células T reguladoras en lupus eritematoso generalizado

“…26,45 Por otra parte, se ha reportado que las células Treg de los pacientes con LEG son capaces de inhibir de manera eficiente la función de los linfocitos B in vitro, mediante un mecanismo que requiere la interacción directa con estas células. 46 Se ha propuesto que los linfocitos T efectores CD4 + CD25de los pacientes con LEG son significativamente menos sensibles al efecto supresor de las células Treg autólogas y de donadores sanos. 18,25 Aunque no se ha caracterizado aún el mecanismo por el cual los linfocitos T efectores de los pacientes con LEG se vuelven resistentes a la función supresora de las células Treg, se ha sugerido el posible papel de la activación del factor de transcripción STAT-3 por la IL-6.…”