Ballesteros_Tato_1Assistant Professor of Medicine

Division of Clinical Immunology and Rheumatology

Address:

Shelby Building, Room 413
1825 University Boulevard
35294

Telephone: (205) 975-4643

Fax: (205) 975-3322

Email: aballest@uab.edu

 

Education:

B.S. (Biology): Vigo University, Spain, 2001
Ph.D. (Microbiology & Immunology): Universidad Autonoma de Madrid, Spain, 2007
Postdoctoral Fellow: Trudeau Institute, Saranac Lake, NY, 2008
Postdoctoral Fellow: University of Rochester, NY, 2008-2012.

 

Research Interests

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 goals of my lab is to determine 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 autoimmune disease. 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.

 

Publications

Click here for a complete list of publications. Below are a few selected papers.


Ballesteros-Tato A
, Randall TD, Lund FE, Spolski R, Leonard WJ, León B. 2016. T Follicular Helper Cell Plasticity Shapes Pathogenic T Helper 2 Cell-Mediated Immunity to Inhaled House Dust Mite. Immunity. 44(2):259-73. PMID: 26825674; PMCID: PMC4758890.


Leon, B., Bradley, J.E., Lund, F.E., Randall, T.D. & Ballesteros-Tato, A. 2014. FoxP3+ regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability. Nature communications 5, 3495 PMID: 24633065 PMCID: PMC4013682


Ballesteros-Tato, A.
, Leon, B., Lund, F.E. & Randall, T.D. CD4+ T helper cells use CD154-CD40 interactions to counteract T reg cell-mediated suppression of CD8+ T cell responses to influenza. 2013 The Journal of Experimental Medicine 210, 1591-1601. PMID: 23835849 PMCID: PMC3727323


Ballesteros-Tato, A, 
 León, B, Graf, BA, Moquin, A, Adams, PS, Lund, FE, Randal, TD. 2012 Interleukin-2 Inhibits Germinal Center Formation by Limiting T Follicular Helper Cell Differentiation.  Immunity. 36: 847-856. PMID:22464171


Ballesteros-Tato, A
, B León, FE. Lund and TD. Randall. 2010. Temporal changes in dendritic cell subsets, cross-priming and costimulation via CD70 control CD8+ T cells responses to influenza. Nat. Immunol. 11:216-224. PMID:20098442 PMCID:PMC2822886

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