Kevan Roberts completed his undergraduate work in Biochemistry at the University of Manchester, UK. He subsequently received his PhD in Immunology under the supervision of Dr. Michael Moore in 1984 while at the Christie Hospital, Manchester, UK. He then completed post-doctoral studies in the Surgery Branch (with Dr. Michael Lotze) and the Laboratory of Immunology (with Dr. Ethan Shevach) at the National Institute of Health, Bethesda, USA and finally the Babraham Institute, Cambridge, UK (with Dr. Peter Kilshaw). He became a Senior Lecturer in Immunology in 1993 at the School of Medicine in Southampton, UK and moved to the University of Montana as an Associate Professor in 2003.
Allergic asthma is characterized by airway hyperresponsiveness and eosinophilic inflammation mediated by CD4+ Th2 cells. That these events arise as a consequence of a defect in immune regulation is implied from the observation that lung mucosal immune responses are normally tightly regulated. However, the specific mechanisms that transpires to resolve, or possibly prevent, airway mucosal Th2-mediated inflammation are poorly understood. Certainly, the production of specific prostanoids and the anti-inflammatory cytokines TGF-b or IL-10 at sites of inflammation serve to limit mucosal immune responses.
The laboratory focuses primarily on the regulation of lung mucosal Th2 responses. Most notably, we are elucidating how prostanoids such as PGI2, generated during allergic pulmonary inflammation, serve to selectively limit the progression of Th2 responses. In addition, we are investigating whether Th2-mediated airway inflammation is influenced by antigen-specific regulatory T cells. Regulatory T cells have been identified in mice and humans as a distinct population of CD4+ T cells that constitutively express the IL-2 receptor (IL-2R) a chain (CD25). CD4+CD25+ T cells play an essential role in the maintenance of peripheral self-tolerance by preventing the activation and proliferation of autoreactive T cells that have escaped thymic deletion. CD4+CD25+ T cells from DO11.10 mice express the transgenic T cell receptor and mediate regulatory activity. We have demonstrated that CD4+CD25+ T cells play a key role in regulating airway eosinophilic inflammation, most notably by limiting the differentiation of a specific proinflammatory CD4+ Th2 phenotype. An understanding of the regulation of Th2 responses will provide better insight into design of novel approaches to modulate the chronic airway inflammation evident in bronchial asthma.
Jaffar Z., Ferrini M.E. and Roberts K. (2007). IL-2 is an essential cytokine for the expansion of Th17 cells in vivo during pulmonary neutrophilic inflammation (pending).
Jaffar Z., Ferrini M.E., Buford M.C., FitzGerald G.A. and Roberts K. (2007). Prostaglandin I2-IP signaling blocks allergic pulmonary inflammation by preventing recruitment o CD4+ Th2 cells into the airways in a mouse model of asthma. J. Immunol. (accepted for publication).
Stanciu, L. A., Roberts, K., Papadopoulos, N. G., Cho, S. H., Holgate, S. T., Coyle, A. J., and Johnston, S. L. (2005) IL-4 increases type 2, but not type 1, cytokine production in CD8+ T cells from mild atopic asthmatics. Respir Res, 6, 67-73.
Jaffar Z., Sivakuru T., and Roberts K. (2004). CD4+CD25+ T cells regulate airway eosinophilic inflammation by modulating the Th2 cell phenotype. J. Immunol. 172, 3842-9.
Jaffar Z., Wan K.-S., and Roberts K. (2002). A key role for PGI2 in limiting lung mucosal Th2 but not Th1 responses to inhaled allergen. J. Immunol. 169:5997-6004.
Roberts K. and Jaffar Z. (2002). Regulation of the adaptive immune response to inhaled allergens. Clin. Exp. Allergy (Rev) 32, 343-344.
Lordan J.L., Davies D.E., Wilson S.J., Dent G., Corkhill A., Jaffar Z., Roberts, K., Djukanovic R., and Holgate, S.T. (2001) . The role of CD28-B7 costimulation in allergen-induced cytokine release by bronchial mucosa from patients with moderately severe asthma. J. Allergy Clin. Immunol. 108:976-81.
Stanciu L.A., Roberts K., Lau C.L.K., Coyle A.J., and Johnston S.L. (2001). Induction of type 2 activity adult human CD8+ T Cells by repeated stimulation and IL-4. Int. Immunol. 13, 341-353.
Lee S.-C., Jaffar Z., Wan K.-S., Holgate S., and Roberts K. (1999). Regulation of pulmonary T cell responses to inhaled antigen: Role in Th1 and Th2-mediated inflammation. J. Immunol. 162:6867-6879.
Jaffar Z., Stanciu L., Pandit A., Lordan J., Holgate S., and Roberts K. (1999). Essential role for both CD80 and CD86 costimulation but not CD40 interactions in allergen-induced Th2 cytokine production from asthmatic bronchial tissue: Role for ?? but not ?? T cells. J. Immunol. 163:6283-6291.
Jaffar Z., Roberts K., Pandit A., Linsley P., Djukanovic R., and Holgate S. (1999). B7 costimulation is required for IL-5 and IL-13 secretion by bronchial biopsy tissue of atopic asthmatic subjects in response to allergen stimulation. Am. J. Resp. Cell Mol. Biol. 20:153-162.
Roberts K., Jaffar Z., Semper A., and Holgate S. (1999). Asthma: Clinical Aspects and Mucosal Immunity. In Mucosal Immunology, edited by P. Ogra, J. Mestecky, M. Lamm, W. Strober, J. Bienenstock, J. McGhee (Acad. Press): chapter 77, p. 1197-1211.
Teran, L. M., Park H.S., Djukanovic R., Roberts K., Holgate S. (1997). Cultured nasal polyps from nonatopic and atopic patients release RANTES spontaneously and after stimulation with phytohemagglutinin. J. Allergy Clin. Immunol. 100:499-504.
Park H. S., Jung K. S., Shute J., Roberts K., Holgate S. T., and Djukanovic R. (1997). Allergen-induced release of GM-CSF and IL-8 in vitro by nasal polyp tissue from atopic subjects prolongs eosinophil survival. Eur. Resp. J. 10:1476-1482.
Roberts K. and Kilshaw P.J. (1993). The mucosal T cell integrin ?IEL?7 recognizes a ligand on mucosal epithelial cell lines. Eur. J. Immunol. 23:1630-1635.
Wilde D., Roberts K., Sturmhoefel K., Kikuchi G., Coligan J., and Shevach E. (1992). Mouse autoreactive ??? T cells. Functional properties of autoreactive T cell hybridomas. Eur. J. Immunol. 22:483-489.
Kikuchi G.E., Roberts K., Shevach E. M., and Coligan J. E. (1992). Gene transfer demonstrates that the V?1.1 C?4 V?6 T cell receptor is essential for spontaneous secretion of lymphokine by ?? T cells. J. Immunol. 148:1302-1307.
Roberts K. and Shevach E. M. (1991). Immunoregulatory role of ?? T cells. Annal. New York Acad. Sci. 636:1-8.
Roberts K., Yokoyama W. M., Kehn P.J., and Shevach E.M. (1991). The vitronectin receptor serves as an accessory molecule for the activation of ????T cells. J. Exp. Med. 173:231-240.
Moulder K., Roberts K., Shevach E. M., and Coligan J.E. (1991). The mouse vitronectin receptor is a T cell activation antigen. J. Exp. Med. 173: 343-347.
Roberts K. and Lotze M.T. (1988). IL-2 promotes conjugate formation by purified LAK precursors and T lymphocytes: evaluation of conjugates using flow cytometric techniques. J. Biol. Resp. Mod. 7: 249-66.