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Rebecca O'Brien PhD

Professor of Immunology & Microbiology


1400 Jackson St., Rm K814
Denver, CO 80206
Phone: 303-398-1158
E-mail: obrienr@njhealth.org
Dr. O'Brien's National Jewish Health webpage

My research concerns the specificity and function of the gamma delta T lymphocytes.  These cells represent a relatively rare type of T cell in mice and humans whose purpose is at this time not well understood.  Other lymphocytes, alpha beta T cells and B lymphocytes, by virtue of their antigen receptors, can detect and eliminate foreign micro-organisms from the body.  The gamma delta T cells also carry T cell receptors (TCRs), related to but distinct from those carried by alpha beta T cells.  However, although they may also be able to recognize foreign molecules, gamma delta TCRs at least in some cases recognize molecules that are produced by our own bodies, which are induced during infection or inflammation and can also be present on tumor cells.  Perhaps because of their ability to respond to self molecules whose expression indicates indicates the presence of a threat to the host, gamma delta T cells have often been found to play a regulatory role, and our laboratory is currently focusing on the role of gamma/ delta T cells in autoimmune disease, through three different projects.

First, we discovered some years ago that many female mice of particular genetic background, when rendered unable to produce gamma delta T cells, develop a severe inflammation of the cornea due to an autoimmune attack.  An investigation of how gamma delta T cells normally suppress this and protect the eye from autoaggression is now in progress.  Recent results suggest that the lack of gamma delta T cells results in a failure to suppress activated and presumably autoreactive CD8+ alpha/beta T cells, probably by inhibiting the development of regulatory alpha/ beta T cell subsets.  Second, in the NOD mouse model of type 1 diabetes we are also investigating a potential role for gamma/ delta T cells.  Because different gamma delta T cell subsets appear to play distinct roles, we are focusing on how removal of particular subsets, defined by expression of certain gamma chain variable regions, affects the development of diabetes.   Third, we discovered that certain gamma/ delta T cells are able to recognize an insulin B chain peptide.  Like alpha/ beta T cells that recognize the same peptide and can be diabetogenic, the gamma/ delta T cells appear to recognize the peptide only when it takes on a particular configuration.  We are currently attempting to determine the components of the gamma/ delta TCR needed to confer recognition of this insulin peptide, and plan to go on to further define the stimulatory peptide configuration as well.

  • O'Brien, R.L., Taylor, M.A., Hartley, J., Nuhsbaum, T., Dugan, S., Lahmers, K., Aydintug, M.K., Roark, C., and Born, W.K.  Protective role of γδ T cells in spontaneous ocular inflammation.  Invest. Ophthal. Vis. Sci. 50:  3266-3274, 2009. PMC2701479
  • French, J.D., Roark, C.L., Born, W.K., and O'Brien, R.L.  T lymphocyte homeostasis is negatively regulated by 2-microglobulin.  J. Immunol.182:  1892-1900, 2009.  (featured in “In this issue.”) PMC2703819
  • Simonian, P.L., Roark, C.L., Wehrmann, F., Lanham, A.M., Born, W.K., O’Brien, R.L., Fontenot, A.P. IL-17A expressing T cells are essential for bacterial clearance in a murine model of hypersensitivity pneumonitis. J. Immunol. 182:  6540-6549, 2009. PMC2766088
  • Huang, Y., Jin, N., Roark, C.L., Aydintug, M.K., Wands, J.M., Huang, H., O'Brien, R.L., Born, W.K. The influence of IgE-enhancing and IgE-suppressive γδ T cells changes with exposure to inhaled ovalbumin. J.  Immunol. 183:  849-855, 2009. PMC27
  • Simonian, P.L., Wehmann, F., Roark, C.L., Born, W.K., O'Brien, R.L., and Fontenot, A.P.  γδ T cells protect against lung fibrosis via IL-22. J. Exp. Med. 207: 2239 – 2253, 2010. PMC2947077
  • O'Brien, R.L., Born, W.K. γδ T cell subsets: A link between TCR and function? Sem. Immunol. 22:  193-198, 2010. PMC2906689
  • O’Brien, R.L., Chain, J.L., Aydintug, M.K., Bohrer-Kunter, D., Huang, Y., Hardy, I.R., Cambier, J.C., Lahmers, K., Nuhsbaum, T., Davidson, R., Sun, D., Born, W.K. αβTCR+ T cells, but not B cells, promote autoimmune keratitis in B10 mice lacking γδ T cells. Invest. Ophthal. Vis. Sci. 53: 301-308, 2012. PMC3292366
  • Roark, C.L., Huang, Y., Jin, N., Aydintug, M.K., Casper, T., Sun, D., Born, W.K., O'Brien, R.L. A canonical Vγ4Vδ4+ γδ T cell population with distinct stimulation requirements which promotes the Th17 response. Immunol. Res. 55:  217-230, 2013.  PMC3543513
  • Huang, Y., Aydintug, M.K., Loomis, J., Macleod, M.K., McKee, A.S., Kirchenbaum, G., Jakubzick, C.V., Kedl, R.M., Sun, D., Jacobelli, J., O'Brien, R.L., Born, W.K. Antigen-specific regulation of IgE antibodies by non-antigen-specific γδ T cells. J. Immunol. 190:  913-921, 2013.  PMC3552125
  • Aydintug, M.K., Zhang, L., Wang, C., Liang, D., Wands, J.M., Michels, A.W., Hirsch, B., Day, B.J., Zhang, G., Sun, D., Eisenbarth, G.S., *O'Brien, R.L., *Born, W.K. γδ T cells recognize the insulin B:9-23 peptide antigen when it is dimerized through thiol  oxidation. Molec. Immunol. 60:  116-128, 2014 (*co-senior seniors). PMC4091716

View of Recent Publications in PubMed

NIH Research Career Development Award, 1994-1999
Winner of the Max and Bessie Regina Schwartz-Weinstein Research Grant, presented by the Arthritis Foundation, Rocky Mountain Chapter, 1999
Winner of the Harmon Award for Outstanding Research, presented by the Arthritis Foundation, Rocky Mountain Chapter, 2000
AITC Study Section (Allergy, Immunology and Transplantation), regular member, 4 year appointment, 2004 - 2008
Faculty of 1000 Member, Advisory Board,  2008-2011
Faculty of 1000 Section Head, Immunity to Infections. June 2011 – present
F1000 Research Advisory Panel Member, May 2012- present