Ciriaco A. Piccirillo
Associate Professor, Immunology;
Member of the Center for
the Study of Host Resistance
Immunoregulation of autoimmune and infectious diseases
Montreal General Hospital
1650 Cedar Avenue
Montreal, QC H3G 1A4
Tel: (514) 934-1934 ext: 45135
Fax: (514) 934-8332
ciro [dot] piccirillo [at] mcgill [dot] ca (Email)
Montreal General Hospital Webpage
Radio Canada article on Dr. Piccirillo (in French)
My research program as Canada Research Chair in Regulatory lymphocytes of the Immune System focuses on the immune regulation of autoimmune and infectious diseases mediated by naturally-occurring CD4+ regulatory T cells (nTreg), a unique population of cells with potent immunosuppressive functions in vitro an in vivo. nTreg cells constitute 1-10% of total CD4+ T cells from thymus, peripheral blood and lymphoid tissues in mice and humans. Functional abrogation of these cells in the host results in the onset of multi-organ-specific autoimmune diseases, and increases immunity to tumors, grafts, and various pathogens. Thus, nTreg cells play a central role in dampening peripheral immune responses, and contribute to the establishment of tolerance by an as-of-yet undefined mechanism.
My laboratory makes use of cutting-edge experimental strategies to characterize the relative contribution of nTreg cells as a determining factor in establishing resistance or susceptibility to autoimmune and infectious diseases. We try to characterize the functional dynamics of nTreg cell activity in human autoimmune diseases (type 1 diabetes) as well as in animal models of autoimmunity (type 1 diabetes), tumors (spontaneous breast cancer), infections (malaria), and mucosal immunity (inflammatory bowel disease). My research program makes use of standard and state-of-the-art molecular, proteomic, biochemical, cellular and imaging approaches to characterize the behavior of nTreg cells in health and disease.
Selected Recent Publications
M. Tritt, E. Sgouroudis, E. d’Hennezel, A. Albanese and *C.A. Piccirillo "Functional waning of naturally-occurring CD4+ regulatory T cells contributes to the onset of autoimmune diabetes." (Diabetes 2007 Oct 10; [Epub ahead of print]) * Senior corresponding author.
Giroux, M., J. St-Pierre, K. Yurchenko, C. A. Piccirillo and C. Perreault "T Regulatory Cells Control Numbers of NK Cells and CD8α+ Immature Dendritic Cells in the Lymph Node Paracortex." J Immunol. 179:4492-502; 2007.
Piccirillo, C.A. "CD4+Foxp3+ regulatory T cells in the negative control of immune responses. Effector CD4+ T Cells in Health and Disease." Songqing Na and Chandrasekar Iyer, Editors. Nova Science Publishers, Inc. New York. (In press, 2007).
Piccirillo, C.A. "CD4+Foxp3+ regulatory T cells in the control of immunological tolerance. Regulatory T cells." Robert Lechler, Ed. Springer Publishers, Inc. New York. (In press, 2007).
Segura, M., Z. Su, C.A. Piccirillo, and M.M. Stevenson "Impairment of dendritic cell function by excretory-secretory products: a potential mechanism for nematode-induced immunosuppression." Euro J. Immunol. 37:1887-904; 2007.
Pyzik M., and *C.A. Piccirillo "TGF-β1 modulates Foxp3 expression and regulatory activity in distinct CD4+ T cell subsets." J Leuko. Biol. 82:335-46; 2007.
K, Yurchenko, M. Tritt, V. Hay, Belkaid Y., and *C.A. Piccirillo "CCR5-dependent recruitment of naturally-occurring CD4+CD25+ regulatory T cells in sites of chronic infection favors pathogen persistence." J. Exp. Med. 203:2451-60; 2006.
Levings, M.K., S.E. Allan, E.d’Hennezel, and C.A. Piccirillo* "Functional dynamics of CD4+FoxP3+ regulatory T cells in health and disease." Adv. In Immunol. 92; 119-155. 2006.
Toda, A. and C.A.Piccirillo* "Development and functions of naturally-occurring CD4+CD25+ regulatory T cells." J. Leuko. Biol. 80, 1-13. 2006.
Pyzik, M. and Piccirillo, C.A. "The TGF-β/Foxp3 regulatory axis in immune tolerance: implications for health and disease." Inflamm Allergy Drug Targets 5:167-177. 2006.
Yurchenko K., H. Friedman, A. Peterson and *C.A. Piccirillo. "Development of a mouse model ubiquitously expressing mRFP-1 by site-directed transgenesis." Transgenic Research 16:29-40; 2006.
Manigold T., K. Mihalik, C.M. Rice, S.M. Feinstone, C. A. Piccirillo, B. Rehermann. "Foxp3+CD4+CD25+ Regulatory T Cells Control virus-specificmemory T cells in chimpanzees that recovered from hepatitis C." Blood 107:4424-4432. 2006
Suffia IJ, Reckling SK, Piccirillo CA, Goldszmid RS, Belkaid Y. "Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens." J. Exp Med. 203, 777-788, 2006.
Piccirillo C.A., A. N. Theofilopoulos, and G. J. Prud’homme "Immunogene therapy with non-viral vectors." Gene Therapy for Atoimmune Disease. G. J. Prud’homme, Ed. Landes Bioscience and Klunes/Plenus Publishers. (2005).
M. Kullberg, V. Hay, A. Sher, J.J. Letterio, E.M. Shevach, and *C.A. Piccirillo "TGFbeta1-independent control of mucosal inflammation mediated by naturally-occurring CD4+CD25+ regulatory T cell in vivo." Eur. J. Immunol. 35:2886–2895, 2005.
Piccirillo, C.A. "Helper and Regulatory T lymphocytes." McGraw-Hill Yearbook of Science and Technology p.134-13, 2005.
Piccirillo, C.A. "Tolerogenic functions of naturally-occurring CD4+CD25+ regulatory T lymphocytes." Altered immunoregulation and human disease: Regulation and development of T cell tolerance, R. Gorzynski, Ed. Publishing House ed. p.165-192, 2005.
*C.A. Piccirillo, M. Tritt, E. Sgouroudis, A. Albanese, M. Pyzik, and V. Hay "Control of type 1 autoimmune diabetes by naturally-occurring CD4+CD25+ regulatory T lymphocytes." Annals of NY. Acad. Sci. 1051:72-87, 2005.
M. Hesse, C. A. Piccirillo, Y. Belkaid, J. Prufer, M. Mentink-Kane, M. Leusink, A. W. Cheever, E. M. Shevach, and T. A. Wynn "CD4+CD25+ regulatory T cells are the major source of host protective IL-10 in murine schistosomiasis." J. Immunol. 172:3157-66, 2004.
A.M. Thornton, C.A. Piccirillo and E.M Shevach "Cytokine and costimulatory requirements for induction of CD4+CD25+suppressor effector function." Euro. J. Immunol. 34:366-76, 2004.
A.M. Thornton, E. Donovan, C.A. Piccirillo and E.M. Shevach "IL-2 is critically required for activation of the suppressor function of CD4+CD25+ T cells in vitro." J. Immunol 172:6519-6523, 2004.
S. Mendez, S. K. Reckling, C. A. Piccirillo, D. Sacks, Y. Belkaid "Role for CD4+CD25+ regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity." J Exp Med. 200:201-10, 2004.
*C.A. Piccirillo and A.M. Thornton "Cornerstone of peripheral tolerance: naturally-occurring CD4+CD25+ regulatory T cells." Trends in Immunol. 25:374-380, 2004.
*C.A. Piccirillo and E.M. Shevach "Naturally-occurring CD4+CD25+ immunoregulatory T cells: Central players in the arena of peripheral tolerance." Semin. Immunol. 16:81-88, 2004.
E.M. Shevach, C. A. Piccirillo, A.M. Thornton and R.S. McHugh "Control of T cell activation by CD4+CD25+ suppressor T cells." Novartis Symposia 252:24-36, 2003.
Ciriaco A. Piccirillo, Ethan M. Shevach, et al. "CD4+CD25+ immunoregulatory T cells: naturally-occurring but adaptable." Nature Reviews in Immunology 3, 2003.
Ciriaco A. Piccirillo and Gérald J. Prud'homme. "Gene therapy with plasmids encoding cytokine- or cytokine receptor-IgG chimeric proteins." Methods in Molecular Medicine: Cytokines and Colony Stimulating Factors; Methods and protocols. Humana Press, 215:153-70, 2003.
Piccirillo C.A. and Prud'homme G.J. "Immune modulation by plasmid DNA-mediated cytokine gene transfer." Current Pharmaceutical Design. 9, 83-94, 2003.
Ciriaco A. Piccirillo, Ethan M. Shevach, et al. "CD4+CD25+ immunoregulatory T cells: naturally-occurring but adaptable." Nature Reviews in Immunology 3., 2003.
McHugh RS, Whitters MJ, Piccirillo CA, Young DA, Shevach EM, Collins M, Byrne MC. "CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor." Immunity 16: 311-323, 2002.
Piccirillo, Ciriaco A., John J. Letterio, Angela M. Thornton, Rebecca S. McHugh, Mizuko Mamura, Hidekazu Mizuhara, and Ethan M. Shevach. "CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness." J. Experimental Medicine. 196:237-246, 2002.
Belkaid, Yasmine *, Ciriaco A. Piccirillo*, Susana Mendez, Ethan M. Shevach and David L. Sacks. "CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity." Nature 420:502-7, 2002. *Equal contribution.
Shevach EM, McHugh RS, Piccirillo CA, Thornton AM. "Control of T-cell activation by CD4+ CD25+ suppressor T cells." Immunological Reviews 182:58-67, 2001.
Piccirillo C.A., Shevach E.M. Cutting edge: Control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells." J. Immunology. 167:1137-1140, 2001.
Shevach EM, McHugh RS, Thornton AM, Piccirillo C, Natarajan K, and Margulies, DM "Control of autoimmunity by regulatory T cells." Mechanisms of Lymphocyte Activation and Immune Regulation VIII. Autoimmunnity: 2000 and Beyond, S. Gupta, Ed. Plenum Press, New York.
Prud'homme G.J. and C.A. Piccirillo "The inhibitory effects of transforming growth factor beta 1 (TGF-beta1) in autoimmune diseases." J. Autoimmunity 14:23-42, 2000.