Autoimmune (type 1) diabetes mellitus results from the destruction of insulin-producing pancreatic β cells by T lymphocytes. Prediction of cell-mediated autoimmune diseases by direct detection of autoreactive T cells in peripheral blood has proved elusive, in part because of their low frequency and reduced avidity for peptide MHC ligands.
Jacqueline D. Trudeau, Carolyn Kelly-Smith, C. Bruce Verchere, John F. Elliott, Jan P. Dutz, Diane T. Finegood, Pere Santamaria, Rusung Tan
In the work presented here, we explored the influence of leptin on the kinetics of experimental autoimmune encephalomyelitis (EAE) onset, in the EAE-associated inflammatory anorexia, and in the development of pathogenic T cell responses. We found that the expression of serum leptin increased before the clinical onset of EAE in disease-susceptible C57BL/6J (H-2b) and SJL/J (H-2s) strains of mice, which are models of chronic-progressive and relapsing-remitting EAE, respectively. This increase in serum leptin correlated with disease susceptibility, reduction in food intake, and decrease in body weight. Indeed, acute starvation, which is able to prevent the increase in serum leptin, delayed disease onset and attenuated clinical symptoms by inducing a T helper 2 cytokine switch. Furthermore, immunohistochemical analysis revealed a parallel in situ production of leptin in inflammatory infiltrates and in neurons only during the acute/active phase of both chronic-progressive and relapsing-remitting EAE. We also found that leptin secretion by activated T cells sustained their proliferation in an autocrine loop, since antileptin receptor antibodies were able to inhibit the proliferative response of autoreactive T cells in vitro. Given that leptin appears to regulate EAE susceptibility, inflammatory anorexia, and pathogenic T-cell immune function, we postulate that it may offer a potential target in the treatment of multiple sclerosis.
Veronica Sanna, Antonio Di Giacomo, Antonio La Cava, Robert I. Lechler, Silvia Fontana, Serafino Zappacosta, Giuseppe Matarese
Nelli Shushakova, Julia Skokowa, Jurriaan Schulman, Ulrich Baumann, Jörg Zwirner, Reinhold E. Schmidt, J. Engelbert Gessner
Takao Ando, Rauf Latif, Alla Pritsker, Thomas Moran, Yuji Nagayama, Terry F. Davies
Neal B. Blatt, Jeffrey J. Bednarski, Roscoe E. Warner, Francesco Leonetti, Kathryn M. Johnson, Anthony Boitano, Raymond Yung, Bruce C. Richardson, Kent J. Johnson, Jonathan A. Ellman, Anthony W. Opipari Jr., Gary D. Glick
Ming-Chao Zhong, Nicole Kerlero de Rosbo, Avraham Ben-Nun
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