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Rebecca O'Brien PhD

Professor of Immunology


 

 

 

 

 

Phone: 303-398-1158
Fax: 303-398-1806
E-mail: obrienr@NJHealth.org 
Dr. O'Brien's National Jewish Health webpage

   

My laboratory is studying gamma/delta T lymphocytes, which are known to be important for immune regulation, resistance to infectious pathogens, and tumor elimination.  These T cells differ from the classical alpha/beta T cells in that they are less abundant in the blood and lymphoid tissues but are common in epithelial sites, and are activated differently than alpha/beta T cells.  Whereas alpha/beta T cell receptors (TCRs) recognize foreign peptides from infectious microbes bound to MHC molecules on other cells, gamma/delta TCRs instead appear to recognize molecules that are produced by our own bodies, whose production is induced during infection or inflammation.  For the most part, these gamma/delta TCR ligands have not yet been defined, which causes a gap in our understanding of how gamma/delta T cell responses are triggered.  Moreover, distinct subsets of gamma/delta T cells, which in some cases can be defined by the variable genes their TCRs express, play different functional roles, and whereas some promote the development of inflammation, others reduce it. 

 

Currently, three projects are on-going my laboratory towards investigating some of the unanswered questions about these cells.  First, a project is underway to discover the ligands for certain common mouse gamma/delta TCRs, carried by gamma/delta T cells that have known effects on various disease models.  The affinity of the gamma/delta TCR for its ligand is expected, like that of the alpha/beta TCR, to be low, and so we have generated self-pentamerizing soluble gamma/delta TCRs, which we are using as reagents to detect their own ligands. Defining common ligands will enable us to carry out functional experiments in which gamma/delta TCR ligands are ablated, to determine how and when the relevant gamma/delta T cells become activated, and what functions they carry out when activated.  Second, we have discovered that mice of a certain background that cannot produce gamma/delta T cells have a high frequency of spontaneous autoimmune disease in the cornea of their eyes.  The immunology of the eye is unique compared to systemic immunity, and we are carrying out tests to determine what gamma/delta T cells normally do in these animals that prevents this eye disease from developing.  Third, we have discovered that several distinct gamma/delta T cell subsets produce IL-17 when activated, a cytokine that strongly promotes neutrophil activation, and are now investigating how these cells and the IL-17 they produce influence the overall immune response during infectious vs. autoimmune disease.  

 

  • Aydintug, M. K., C. L. Roark, X. Yin, J. M. Wands, W. K. Born, and R. L. O'Brien. 2004. Detection of cell surface ligands for the γδ TCR using soluble TCRs. J. Immunol. In press.
  • O'Brien, R. L., M. L. Lahn, W. K. Born, and S. A. Huber. 2001. TCR and function co-segregate in γδ T cell subsets. Chemical Immunology: γδ T cells. Karger, Basel Ed. A. Takashima and P. Bergstresser:1-28.
  • Huber, S. A., D. A. Graveline, W. K. Born, and R. L. O'Brien. 2001. Cytokine production by Vγ + T cell subsets is an important factor determining CD4 Th-cell phenotype and susceptibility of BALB/c mice to coxsackievirus B3-induced myocarditis. J. Virol. 75:5860-5869.
  • Huber, S. A., D. Graveline, M. K. Newell, W. K. Born, and R. L. O'Brien. 2000. Vγ 1+ T cells suppress and Vγ 4+ T cells promote susceptibility to coxsackievirus B3-induced myocarditis in mice. J. Immunol. 165:4174-4181.
  • Mukasa, A., W. K. Born, and R. L. O'Brien. 1999. Inflammation alone evokes the response of a TCR-invariant mouse γδ T cell subset. J. Immunol. 162:4910-4913.


View of Recent Publications in PubMed

Rebecca L. O'Brien, P.I.
Christina Roark, Instructor
M. Kemal Aydintug, Research Associate
Jena French, Postdoctoral Fellow
Xiang Yin, Laboratory Technician

Willi Born, Ph.D. (National Jewish Health)
John Kappler, Ph.D. (National Jewish)
Sally Huber, Ph.D. (Univ. of Vermont)