Dissecting the effector function of pathogenic Tfh cells in human lupus

A subset of T lymphocytes, follicular B helper T cells, or Tfh cells, is necessary to provide help for B lymphocytes in their production of autoantibodies (ANAs) in systemic lupus erythematosus (SLE, lupus). Much remains to be learned about the biology of the former, including the requirements for their maturation and function, and how to interrupt their collaboration with B lymphocytes as a potential therapy for autoimmune diseases such as SLE. We do know that Tfh cells produce proteins, called cytokines, which are critical for activating B cells in lupus with production of autoantibodies, and subsequent inflammation in organs of patients. Recently we developed a novel technique, called a multiplexed cytokine profiling microchip, to detect the cytokines made by Tfh cells in lupus, using a small sample of blood from patients. We can now use this new technique to fully characterize Tfh cells, including the cytokines they use to induce autoantibody formation by B cells that injure tissues, the means by which these cytokines are produced within the cell, and to follow the effects of treatments for lupus, which we will also do in our proposed study. The results of our project should advance knowledge of how lupus develops in humans, and how to monitor patients during treatment and treatment effectiveness.