Research ArticleType I Diabetes

Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients

See allHide authors and affiliations

Science Translational Medicine  25 Jan 2012:
Vol. 4, Issue 118, pp. 118ra12
DOI: 10.1126/scitranslmed.3003401

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Gut Reaction

The immune system is tasked with protecting the body from foreign invaders; however, sometimes the body itself is perceived as foreign. One such case is type 1 diabetes, where the immune system attacks and destroys the insulin-producing β cells of the pancreas. An immunomodulatory drug, teplizumab, is currently being tested in clinical trials for new-onset type 1 diabetes on the basis of encouraging preclinical and phase 1 studies. However, data from the early trials did not confirm the proposed mechanism of action from the preclinical studies. Using a humanized mouse model, Waldron-Lynch et al. now identify a mechanism that is consistent with type 1 diabetes patients treated with teplizumab.

Teplizumab is a humanized non–Fc-binding antibody to CD3—a molecule critical for T cell activation. Waldron-Lynch et al. found that in humanized mice, teplizumab causes certain T cells that express the gut-homing receptor CCR6 to leave the circulation and migrate to the gut. While there, these cells begin producing a regulatory cytokine, IL-10; these cells then return to circulation. These IL-10–producing CCR6+ cells were also found in the blood of type 1 diabetes patients after teplizumab treatment. By allowing examination of human immune cells without the restrictions of looking in human subjects, observations of humanized mice should improve the design—and hopefully increase the chances of success—of future clinical trials.

View Full Text

Stay Connected to Science Translational Medicine