Dr. Ballesteros-Tato is exploring an important interaction between two different cell types of the immune system as a new avenue for targeted drug development in lupus. Specialized immune cells—T follicular helper (Tfh) cells—act as a support system to aid and nurture the B cells, a cell type that produce self-damaging antibodies. It is these antibodies that attack the bodies of people with lupus, damaging their kidneys, brain, skin, and other organs. Dr. Ballesteros-Tato will use his Novel Research Grant to look for ways to selectively eliminate Tfh cells without knocking out other types of T cells that are part of a healthy immune system. He expects that such a treatment would, in turn, power down lupus-related B cells and block disease progression.

What this study means for people with lupus

Currently, no treatments can break the bond between Tfh cells and B cells in people with lupus. Dr. Ballesteros-Tato’s research focuses on this interesting pathway and may lead to innovative directions for the development of new drugs that can add to the therapy arsenal for people with lupus.

Although the underlying mechanisms that drive SLE remain unclear, autoreactive antibodies are thought to play a major role in disease progression. Importantly, the expansion of CD4+ T follicular helper (Tfh) cells, a specialized subset of CD4+ T cells that provide survival and differentiation signals to the B cells, contributes to auto-antibody production and correlates with disease activity in murine and human SLE. As such, the blockade of Tfh cell products prevents auto-Ab production and disease progression in preclinical animal models, thus suggesting that targeting Tfh cells may be a good strategy for treating SLE. Unfortunately, there are currently no therapies to selectively deplete Tfh cells in vivo. Therefore, it is essential that we develop therapeutic new strategies to prevent self-reactive Tfh cell responses in SLE patients. In this proposal, we will prove the concept of a novel mechanism-based immunotherapy to selectively deplete Tfh cells and prevent Ab-dependent autoimmune pathology in SLE patients without the risk of inducing profound immunosuppression.