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Faculty Detail    
Name ANDRE BALLESTEROS-TATO
Assistant Professor
 
Campus Address SHEL 310
Phone  (20-5) -643
E-mail  aballest@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Medicine  Med - Immunology/Rheumatology Associate Professor
Center  Center for AIDS Research  Center for AIDS Research Associate Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Associate Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Associate Professor

Biographical Sketch 
I completed my PhD in Molecular Biology at the Autonoma University of Madrid in Spain in July 2007. In my PhD thesis work, I studied the role of the cell cycle inhibitor p21 and the apoptosis-inducing Fas receptor in controlling immunological tolerance in different murine and human autoimmune diseases. Beginning in March of 2008, I 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, I studied how dendritic cell (DC) subsets responded to influenza infection and how they controlled CD8+ T cell priming and promoted memory T cell differentiation. These previous studies have stimulated my interest in how cells of the innate immune system, particularly DCs, monocytes and their progeny, control both early inflammation and ultimately T and B cell responses to pathogens. I joined the University of Alabama as a Tenure Track assistant professor in June 2015. The focus of the research in my laboratory is to study the cellular interactions, the environmental cues and the molecular mechanisms that control the differential capacity of distinct populations of DCs to regulate T and B cells responses in different models of infection, tumors and autoimmune diseases.



Research/Clinical Interest
Title
Description
The generation of long-lived, high affinity antibodies is required for protective immunity to most viruses and for protection after vaccination. Thus, it is essential to understand the mechanisms that control the generation of long-lasting protective antibody (Ab) responses. T follicular helper (Tfh) cells, a distinct CD4+ T cell subset that expresses high levels of CXCR5 and localizes in the B cell follicles, play an essential role on promoting long-lived Ab responses. In fact, in the absence of Tfh cells, long-term Ab responses are impaired and protection to pathogens compromised. Therefore, it is essential that we understand how to manipulate Tfh responses in order to improve the efficacy of vaccines.However, despite significant advances in the field, our understanding of how Tfh cells responses are initiated is very limited. Recent studies suggest that Tfh cells are initially primed by dendritic cells (DCs), suggesting that we may be able to develop adjuvants that preferentially activate DCs to promote Tfh cell priming or target vaccine antigens to those DCs that preferentially induce Tfh cells. Unfortunately, we do not know what signals direct the DCs to promote Tfh cell differentiation or which specific subsets of DCs prime Tfh cell responses. Thus, one of the projects in my lab is to study the cellular interactions, the environmental cues and the molecular mechanisms that control the differential capacity of distinct populations of DCs to regulate Tfh cell responses in different models of infection and cancer. This knowledge will help us to determine the nature of adjuvants that can be used to boost Tfh cell responses to tumors, pathogens and vaccines. A second project in my lab focuses on the potential clinical benefits of low-dose IL-2 administration to treat autoimmune disease and the mechanisms underlying these effects. Recent studies indicate that low-dose IL-2 treatment suppresses unwanted immune responses in mice and humans, thus evidencing the potential of IL-2 to treat autoimmune disorders (reviewed by us in Immunotherapy. 2014). Increased regulatory T cell activity is one of the potential mechanisms by which low-dose IL-2 immunotherapy induces immunosuppression. However data obtained in my lab indicate that exogenous IL-2 administration prevents aberrant accumulation of Tfh and GC B cell in lupus-prone mice. Our results demonstrate an unexpected immunosuppressive function of IL- 2 that is independent on its role on Treg homeostasis, and provide an alternative mechanism to explain the clinical benefits of IL-2 immunotherapies to treat antibody-mediated autoimmune disorders. These data 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. We 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.

Keywords
Immunology, Microbiology, Infectious Diseases, Autoimmune Disease, Cancer, Dendritic cells, Tfh cells, Lupus, Influenza, IL-2