CD8+ T cells are critical for the clearance of infection through their ability to specifically eliminate infected host cells, and their generation is a tightly regulated process. While my PhD studies focussed on the epigenetic changes that occur during CD8+ T cells differentiation, I am now interested in how stromal cells co-ordinate the development of these immune responses in the lymph node.
Lymph node structure is maintained by a network of chemokine-producing stromal cells that regulate T and B cell localisation in resting lymph nodes. Stromal cells are increasingly understood to play significant roles in regulating the development of immune responses in the lymph node, although these functions are not well defined. I am interested in how one subset of stromal cells, the fibroblastic reticular cells (FRCs), adapt to their changing environment during infection and how this directs the generation of anti-viral immune responses.
epigenetics ; lymph nodes ; B cells ; T cells ; stromal immunology ; localisation ; differentiation ; CD8+ ; memory cells ; CTL ; cytokines
Denton AE, Roberts EW, Linterman MA, Fearon DT.Fibroblastic reticular cells of the lymph node are required for retention of resting but not activated CD8+ T cells. Proc Natl Acad Sci U S A. 2014 Aug 4. pii: 201412910
Roberts EW, Deonarine A, Jones JO, Denton AE, Feig C, Lyons SK, Espeli M, Kraman M, McKenna B, Wells RJ, Zhao Q, Caballero OL, Larder R, Coll AP, O'Rahilly S, Brindle KM, Teichmann SA, Tuveson DA, Fearon DT. Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia. J Exp Med. 2013 Jun 3;210(6):1137-51.
Brendan E. Russ, Alice E. Denton, Lauren Hatton, Hayley Croom, Matthew R. Olson and Stephen J. Turner. Defining the molecular blueprint that drives CD8+ T cell differentiation in response to infection Frontiers in Immunology, 19 December 2012 | doi: 10.3389/fimmu.2012.00371
Denton AE, Russ BE, Doherty PC, Rao S, Turner SJ. Differentiation-dependent functional and epigenetic landscapes for cytokine genes in virus-specific CD8+ T cells. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15306-11
Denton AE, Wesselingh R, Gras S, Guillonneau C, Olson MR, Mintern JD, Zeng W, Jackson DC, Rossjohn J, Hodgkin PD, Doherty PC, Turner SJ. Affinity thresholds for naive CD8+ CTL activation by peptides and engineered influenza A viruses. J Immunol. 2011 Dec 1;187(11):5733-44.
Croom HA, Denton AE, Valkenburg SA, Swan NG, Olson MR, Turner SJ, Doherty PC, Kedzierska K. Memory precursor phenotype of CD8+ T cells reflects early antigenic experience rather than memory numbers in a model of localized acute influenza infection. Eur J Immunol. 2011 Mar;41(3):682-93.
Juelich T, Sutcliffe EL, Denton A, He Y, Doherty PC, Parish CR, Turner SJ, Tremethick DJ, Rao S. Interplay between chromatin remodeling and epigenetic changes during lineage-specific commitment to granzyme B expression. J Immunol. 2009 Dec 1;183(11):7063-72.
Denton AE, Doherty PC, Turner SJ, La Gruta NL. IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8+ T cells. Eur J Immunol. 2007 Feb;37(2):368-75.