BIOSKETCH AND RESEARCH INTERESTS

Dr. André Ballesteros-Tato received his Ph.D. in Molecular Biology from the Autonoma University of Madrid in Spain in July 2007. For his thesis work, he studied the role of the cell cycle inhibitor, p21, and the apoptosis-inducing receptor, Fas, in controlling immunological tolerance in murine and human autoimmune diseases. In 2008, he joined the laboratory of Dr. Troy Randall at Trudeau Institute as a postdoctoral fellow, and then later moved with Dr. Randall's lab to the University of Rochester. As a postdoc, he studied how dendritic cell (DC) subsets responded to influenza infection and how they controlled CD8+ T cell priming and promoted memory T cell differentiation. After joining the Department of Medicine at UAB as an Assistant Professor in June 2015, Dr. Ballesteros-Tato continued his studies of T cell responses, this time focusing on CD4+ T cells and their ability to differentiate into various types of T helper cells following exposure to pathogens, allergens and autoantigens.

Dr. Ballesteros-Tato’s lab is currently focused on understanding the differentiation of CD4 T cell into T follicular helper cells, which are the cells that help B cells produce antibodies. One aspect of these studies is to determine which populations of dendritic cells prime antigen-specific Tfh cell responses. Given that dendritic cells are the first sensors of antigen, the way in which they are activated will dictate the type of T cells that they will prime. Therefore, understanding the types of dendritic cells that prime T follicular helper cells will allow us to determine what types of adjuvants can be used to boost Tfh cell responses in the context of vaccination in order to promote robust, long-lived, high-affinity antibody responses.

Another aspect of these studies is the role of IL-2 in regulating the differentiation of T follicular helper and T regulatory cells, both in the context of vaccination and productive immunity as well as in the context of autoimmunity and pathogenic antibody responses. Recent studies indicate that low-dose IL-2 treatment suppresses T follicular helper and B cell immune responses in both mice and humans, demonstrating the potential of IL-2 to treat autoimmune disorders. Increased regulatory T cell activity is one of the potential mechanisms by which low-dose IL-2 immunotherapy induces immunosuppression. However, data obtained in Dr. Ballesteros-Tato’s lab indicate that exogenous IL-2 administration prevents aberrant accumulation of Tfh and GC B cell in lupus-prone mice. His results demonstrate an unexpected immunosuppressive function of IL- 2 that is independent on its role in Treg homeostasis and provide an alternative mechanism to explain the clinical benefits of IL-2 immunotherapies to treat antibody-mediated autoimmune disorders. He are now exploring the potential therapeutic use of low doses of IL-2 in systemic lupus erythematosus, the potential synergistic effects of combining IL-2 administration with blockade of cytokine pathways that promote Tfh cell development and/or deplete B cells, and how more specifically target IL-2 to Tfh cells. These data will offer new insights into how polymorphisms in the IL-2 and IL-2R genes can affect self-reactive Tfh and B cell responses and influence the development of autoimmune disease manifestations

ABSTRACT

Exposure to environmental antigens, such as house dust mite (HDM), often leads to T helper 2 (Th2) cell-driven allergic responses. However, the mechanisms underlying the development of these responses are incompletely understood. We found that the initial exposure to HDM did not lead to Th2 cell development but instead promoted the formation of interleukin-4 (IL-4)-committed T follicular helper (Tfh) cells. Following challenge exposure to HDM, Tfh cells differentiated into IL-4 and IL-13 double-producing Th2 cells that accumulated in the lung and recruited eosinophils. B cells were required to expand IL-4-committed Tfh cells during the sensitization phase, but did not directly contribute to disease. Impairment of Tfh cell responses during the sensitization phase or Tfh cell depletion prevented Th2 cell-mediated responses following challenge. Thus, our data demonstrate that Tfh cells are precursors of HDM-specific Th2 cells and reveal an unexpected role of B cells and Tfh cells in the pathogenesis of allergic asthma.

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