| RESEARCH SUMMARY
The research in our laboratory is directed at understanding the molecular mechanisms controlling the activation of both NK and NK T cells. These two subsets of cells respond quickly to a stimulus and their activation can determine the outcome of an immune response.
Mammals rely on cytotoxic lymphocytes to recognize and destroy infected cells. Natural killer
(NK) cells provide early innate immune recognition and cytolytic response through granule-mediated killing. Additionally, NK cells secrete direct anti-viral as well as immune regulatory cytokines and chemokines, which can promote non-cytolytic pathogen targeting as well as enhance the cytolytic mechanisms and modulate subsequent immune functions. Their rapid activation has become a hallmark of their potency as innate immune system effectors, positioning NK cells as vital players in viral defense. Furthermore, during the response to infectious agents, changes in receptor expression patterns strongly suggest a critical role for activating and inhibitory receptors in the proper regulation of NK cells. We recently demonstrated that the Killer Lectin-Like Receptor G1 (KLRG1) is induced on NK cells during NK cell activation and that NK cell functions can be inhibited by KLRG1. KLRG1 molecule is a recently described C-type lectin inhibitory receptor expressed on resting NK cells and memory T cells. Determination of the precise role of KLRG1 molecule in regulating NK and T cell functions is actively investigated in the laboratory.
Initiation and propagation of the immune response is the result of a series of coordinated cellular and biochemical interactions that lead to the activation of multiple cell types. It is now clear that an optimal immune response requires a precise and rapid communication between different cell subsets. This phenomenon, referred to as cross-talk, is believed to be an essential component of the immune response that provides necessary inflammatory mediators and cytolytic activity for controlling infections and diseases. An example of an effective cooperation between different cell types has been recently illustrated by the finding that specific activation of CD1 restricted NK T cells can quickly lead to the activation of other subsets of cells such as NK and CD8 T cells. We are currentlypursuing studies focused on elucidating the mechanism of communication between activated NK T cells and NK cells during viral infection. Modulation of the immune function of these cells could have important implications for the generation of an appropriate immune response to pathogens.
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PUBLICATIONS
Anfossi N., S H. Robbins, S. Ugolini, P. Georgel, K. Hoebe, C. Bouneaud, C. Ronet, A. Kaser, C. B. DiCioccio, E. Tomasello, R. S. Blumberg, B. Beutler, S. Reiner, L. A., O. Lantz, D. H. Raulet, L. Brossay and E. Vivier. 2004. Induction and function of CD8+ T cells expressing Ly49 inhibitory receptors specific for MHC class I molecules. J Immunology, in press
Robbins, S. H., M. S. Tessmer, T. Mikayama, and L. Brossay. 2004. Expansion and Contraction of the NK Cell Compartment in Response to MCMV Infection. J Immunology. 173: 259-266
Eash S., R. Tavares, E. G. Stopa, S. H. Robbins, L. Brossay, and W. J. Atwood. 2004. Differential Distribution of the JC Virus Receptor-Type Sialic Acid in Normal Human Tissues. American J. of Pathology. 164:419-428
Wesley J., and L. Brossay. 2003. NK and NK T cells. A two ways cross talk. Archivum Immunologiae et Therapiae Experimentalis. 51: 121-126
Maverakis, E., J. Beech, D. B. Stevens, A. Ametani, L. Brossay, P. van den Elzen, R. Mendoza, Q. Thai, L. H. Macias, D. Ethell, C. W. Campagnoni, A. T. Campagnoni, A. Sette, and E. E. Sercarz. 2003. Autoreactive T cells can be protected from tolerance induction through competition by flanking determinants for access to class II MHC. Proc. Natl. Acad. Sci. U. S. A. 100: 5342-5347
Robbins, S. H., S. C. Terrizzi, T. Mikayama, B. C. Sydora, and L. Brossay. 2003. Differential regulation of KLRG1 expression on T cells. J. Immunol. 170: 5876-5885
Rhee R. J., S. Carlton, J. L. Lomas, C. Lane, L. Brossay, W. G. Cioffi, and A. Ayala. Inhibition of CD1d activation suppresses septic mortality: a role for NK-T cells in septic immune dysfunction. J Surg Res. 2003 115:74-81.
Robbins, S. H. K. B. Nguyen, N. Takahashi, T. Mikayama, C. A. Biron and L. Brossay. 2002. Inhibitory Functions of the Killer Lectin-Like Receptor G1 Molecule during the Activation of Murine NK Cells. J. Immunol. 168: 2585-2589. Cutting Edge report.
Robbins, S.H., and L. Brossay. 2002. Forum: NK Cell Receptors: Emerging Roles in Host Defense Against Infectious Agents. Microbes and Infection. 4:1523-1530
Prigozy, T., O. Naidenko, P. Qasba, D. Elewaut, L. Brossay, T. Natori, Y. Koezuka, A. Kulkarni and M. Kronenberg. 2001. Processing of carbohydrates is required for glycolipid antigen presentation by CD1d molecules. Science 291: 664-667.
Biron, C. A., and L. Brossay. 2001. NK cells and NKT cells in innate defense against viral infections. Current Opinion in Immunology 13:458-464.
Burdin, N., L. Brossay, M. Degano, H. Iijima, M. Gui, I. A. Wilson, and M. Kronenberg. 2000. Structural requirements for antigen presentation by mouse CD1. Proc. Natl. Acad. Sci. U. S. A. 97: 10156-10161.
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LAB MEMBERS
Céline Fugere, Senior Research Assistant
Stephanie Terrizzi, Senior Research Assistant
Katie Heflin, Pathobiology Graduate Student
Marlowe Tessmer, Pathobiology Graduate Student
Johnna Wesley, Pathobiology Graduate Student
Jorge Barrios, Undergraduate Student
Joseph Carpenter, Undergraduate Student
Scott Robbins, Honorary Brossay lab member
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