Islet transplantation in patients with autoimmune diabetes induces homeostatic cytokines that expand autoreactive memory T cells
Open Access
- 1 April 2008
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 118 (5), 1806-1814
- https://doi.org/10.1172/JCI35197
Abstract
Successful transplantation requires the prevention of allograft rejection and, in the case of transplantation to treat autoimmune disease, the suppression of autoimmune responses. The standard immunosuppressive treatment regimen given to patients with autoimmune type 1 diabetes who have received an islet transplant results in the loss of T cells. In many other situations, the immune system responds to T cell loss through cytokine-dependant homeostatic proliferation of any remaining T cells. Here we show that T cell loss after islet transplantation in patients with autoimmune type 1 diabetes was associated with both increased serum concentrations of IL-7 and IL-15 and in vivo proliferation of memory CD45RO+ T cells, highly enriched in autoreactive glutamic acid decarboxylase 65–specific T cell clones. Immunosuppression with FK506 and rapamycin after transplantation resulted in a chronic homeostatic expansion of T cells, which acquired effector function after immunosuppression was removed. In contrast, the cytostatic drug mycophenolate mofetil efficiently blocked homeostatic T cell expansion. We propose that the increased production of cytokines that induce homeostatic expansion could contribute to recurrent autoimmunity in transplanted patients with autoimmune disease and that therapy that prevents the expansion of autoreactive T cells will improve the outcome of islet transplantation.This publication has 38 references indexed in Scilit:
- Expansion and tissue infiltration of an allospecific CD4+CD25+CD45RO+IL-7Rαhigh cell population in solid organ transplant recipientsThe Journal of Experimental Medicine, 2007
- An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cellsThe Journal of Experimental Medicine, 2005
- The new paradigm of T-cell homeostatic proliferation-induced autoimmunityTrends in Immunology, 2005
- Interleukin-12-induced Interferon-γ Production by Human Peripheral Blood T Cells Is Regulated by Mammalian Target of Rapamycin (mTOR)Online Journal of Public Health Informatics, 2005
- Heterologous immunity and homeostatic proliferation as barriers to toleranceCurrent Opinion in Immunology, 2004
- Homeostatic Expansion of T Cells during Immune Insufficiency Generates AutoimmunityCell, 2004
- Interleukin 7 Regulates the Survival and Generation of Memory CD4 CellsThe Journal of Experimental Medicine, 2003
- Increased Thymic Output during Acute Measles Virus InfectionJournal of Virology, 2003
- Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokinesBlood, 2003
- Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes.The Journal of Experimental Medicine, 1995