Follicular T Helper Cells: A New Marker of Type 1 Diabetes Risk?

The incidence of type 1 diabetes (T1D) is increasing at an alarming rate, particularly in young children, and a better understanding of the immune response that triggers this condition is urgently required. A consistent immune feature in many individuals is the appearance of autoantibodies against pancreatic islet antigens, and this can precede the onset of diabetes by many years. Monitoring the autoantibody response is of considerable predictive value, with seroconversion to multiple islet autoantibodies incurring a high risk of future T1D development (1), particularly if the autoantibodies are of high affinity (2). Islet autoantibodies are produced by B cells in a manner that generally requires the help of specialized CD4+ T cells. Exciting recent progress in immunology has generated a new molecular definition of the T cells that provide this help, now called follicular T helper cells (Tfh) (reviewed in ref. 3) (Fig. 1 A ). Importantly, it has been established that Tfh can give rise to a memory population that circulates in peripheral blood and can be identified on the basis of particular surface markers including CXCR5 (the chemokine receptor that attracts T cells to B-cell follicles), ICOS, and PD-1 (4). This has changed the landscape for immune monitoring in diseases characterized by autoantibody production, and elevations in Tfh have been reported in a number of autoimmune conditions including systemic lupus erythematosus, rheumatoid arthritis, and autoimmune thyroid disease (reviewed in ref. 3). It has recently …