Research Themes

Research conducted at the CCIR is conceptually organized into six highly integrated research themes encompassing basic, translational and clinical immunology research. The first three themes focus on the key basic immunology research areas critical for understanding the regulation of innate and adaptive immune responses, while the remaining themes translate these discoveries into understanding the cellular and molecular mechanisms of UV-induced skin cancer and developing more effective immunotherapy for hematological malignancies and solid tumors.

Research Theme 1: Immune Receptors and Signaling

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Objective: Elucidate how immune receptors and signaling regulate immunity and tolerance

Relevant Publications

• Zhang Y, Blattman JN, Kennedy NJ, Duong J, Nguyen T, Wang Y, Davis RJ, Greenberg PD, Flavell RA, Dong C. Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5. Nature 2004, 430(7001): 793-797.
• Cao W, Rosen DB, Ito T, Bover L, Bao M, Watanabe G, Yao Z, Zhang L, Lanier LL, Liu YJ. Plasmacytoid dendritic cell-specific receptor ILT7-Fc epsilon RI gamma inhibits Toll-like receptor-induced interferon production. J Exp Med. 2006, 203(6): 1399-405.
• Ito T, Wang YH, Duramad O, Hanabuchi S, Perng OA, Gilliet M, Qin FX, Liu YJ. OX40 ligand shuts down IL-10-producing regulatory T cells. Proc Natl Acad Sci U S A. 2006, 103(35): 13138-43.
• Nurieva R, Thomas S, Nguyen T, Martin-Orozco N, Wang Y, Kaja MK, Yu XZ, Dong C. T-cell tolerance or function is determined by combinatorial costimulatory signals. EMBO J. 2006, 25(11): 2623-33.
• Zhang Y, Chung Y, Bishop C, Daugherty B, Chute H, Holst P, Kurahara C, Lott F, Sun N, Welcher AA, Dong C. Regulation of T cell activation and tolerance by PDL2. Proc Natl Acad Sci U S A. 2006, 103(31): 11695-700.
• Cao W, Zhang L, Rosen DB, Bover L, Watanabe G, Bao M, Lanier LL, Liu YJ. BDCA2/Fc epsilon RI gamma complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells. PLoS Biol. 2007,  5(10): e248.
• Esashi E, Wang YH, Perng O, Qin XF, Liu YJ, Watowich SS. The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8. Immunity. 2008, 28(4): 509-20.
• Cao W, Bover L, Cho M, Hanabuchi S, Bao M, Rosen DB, Wang Y-H,Shaw JL, Du Q, Arai N, Yao Z, Lanier LL, Liu Y-J. Regulation of TLR7/9 Responses in Plasmacytoid Dendritic Cells by BST2 and ILT7 Receptor Interaction. J Exp Med 2009, 206(7): 1603-14.
• Chang M, Jin W, Sun SC. Peli1 facilitates TRIF-dependent Toll-like receptor signaling and proinflammatory cytokine production. Nat Immunol 2009, 10(10): 1089-95.
• Chung Y, Chang SH, Martinez GJ, Yang XO, Nurieva R, Kang HS, Ma L, Watowich SS, Jetten AM, Tian Q, Dong C. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 2009, 30(4): 576-87.
• Hegde S, Ni S, He S, Yoon D, Feng GS, Watowich SS, Paulson RF, Hankey PA. Stat3 promotes the development of erythroleukemia by inducing Pu.1 expression and inhibiting erythroid differentiation. Oncogene 2009, 28(38): 3349-59.
• Liu X, Alexiou M, Martin-Orozco N, Chung Y, Nurieva R, Ma L, Tian Q, Kollias G, Lu S, Graf D and Dong C. Cutting edge: A critical role of BTLA in peripheral T cell tolerance induction. J Immunol 2009, 182(8): 4516-4520.
• Leitner J, Klauser C, Pickl WF, Stockl J, Majdic O, Bardet AF, Kreil DP, Dong C, Yamazaki T, Zlabinger G, Pfistershammer K, Steinberger P. B7-H3 is a potent inhibitor of human T cell activation: No evidence for B7-H3 and TREML2 interaction. Eur J Immunol 2009, 39(7): 1754-1764.
• Wang Y, Li D, Nurieva R, Yang J, Sen M, Carreño R, Lu S, McIntyre BW, Molldrem JJ, Legge GB, Ma Q. LFA-1 affinity regulation is necessary for the activation and proliferation of naive T cells. J Biol Chem 2009, 284(19): 12645-53.
• Zhang YL, Reynolds JM, Chang SH, Martin-Orozco N, Chung Y, Nurieva RI, Dong C. MKP-1 Is Necessary for T Cell Activation and Function. J Biol Chem 2009, 284 (45): 30815-24.

Research Theme 2: Dendritic Cell Biology

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Objective: Understand how dendritic cells capture, process and present antigens to T cells, link innate and adaptive immune responses and regulate immune tolerance versus immune activation

Relevant Publications

• Watanabe N, Hanabuchi S, Soumelis V, Yuan W, Ho S, de Waal Malefyt R, Liu YJ. Human thymic stromal lymphopoietin promotes dendritic cell-mediated CD4+ T cell homeostatic expansion. Nat Immunol. 2004, 5(4): 426-34.
• Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, Liu YJ. Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 2005, 436(7054): 1181-5.
• Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Wang YH, Su B, Nestle FO, Zal T, Mellman I, Schröder JM, Liu YJ, Gilliet M. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 2007, 449(7162): 564-9.
• Stonier SW, Ma LJ, Castillo EF, Schluns KS. Dendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation. Blood. 2008, 112(12): 4546-54.
• Castillo EF, Stonier SW, Frasca L, Schluns KS. Dendritic cells support the in vivo development and maintenance of NK cells via IL-15 trans-presentation. J Immunol 2009, 183(8): 4948-56.
• Esashi E, Watowich SS. Dendritic cells: transcriptional control of plasmacytoid dendritic cell development by E2-2. Immunol Cell Biol 2009, 87(1): 1-2.
• Fontenot D, He H, Hanabuchi S, Nehete PN, Zhang M, Chang M, Nehete B, Wang YH, Wang YH, Ma ZM, Lee HC, Ziegler SF, Courtney AN, Miller CJ, Sun SC, Liu YJ, Sastry KJ. TSLP production by epithelial cells exposed to immunodeficiency virus triggers DC-mediated mucosal infection of CD4+ T cells. Proc Natl Acad Sci U S A 2009, 106(39): 16776-81.
• Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, Homey B, Barrat FJ, Zal T, Gilliet M. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med 2009, 206(9): 1983-94.
• Lu N, Wang YH, Wang YH, Arima K, Hanabuchi S, Liu YJ. TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell homeostasis. J Exp Med 2009, 206(10): 2111-9.
• Arima K, Watanabe N, Hanabuchi S, Chang M, Sun SC, Liu YJ. Distinct signal codes generate dendritic cell functional plasticity. Sci Signal. 2010, Jan 19;3(105):ra4.

Research Theme 3: T Cell Biology

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Objective: Understand the underlying cellular and molecular mechanisms that regulate the generation and function of effector and memory T cells

Relevant Publications

• Schluns KS, Klonowski KD, Lefrançois L. Transregulation of memory CD8 T-cell proliferation by IL-15Ralpha+ bone marrow-derived cells. Blood 2004, 103(3): 988-94.
• Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005, 6(11): 1133-41.
• Yachi PP, Ampudia J, Gascoigne NR, Zal T. Nonstimulatory peptides contribute to antigen-induced CD8-T cell receptor interaction at the immunological synapse. Nat Immunol. 2005, 6(8): 785-92.
• Stoklasek TA, Schluns KS, Lefrançois L. Combined IL-15/IL-15Ralpha immunotherapy maximizes IL-15 activity in vivo. J Immunol. 2006, 177(9): 6072-80.
• Wang YH, Ito T, Wang YH, Homey B, Watanabe N, Martin R, Barnes CJ, McIntyre BW, Gilliet M, Kumar R, Yao Z, Liu YJ. Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Immunity 2006, 24(6): 827-38.
• Angkasekwinai P, Park H, Wang YH, Wang YH, Chang SH, Corry DB, Liu YJ, Zhu Z, Dong C. Interleukin 25 promotes the initiation of proallergic type 2 responses. J Exp Med. 2007,  204(7): 1509-17.
• Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, Schluns K, Tian Q, Watowich SS, Jetten AM, Dong C. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 2007, 448(7152): 480-3.
• Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, Hippe A, Corrigan CJ, Dong C, Homey B, Yao Z, Ying S, Huston DP, Liu YJ. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. J Exp Med. 2007, 204(8): 1837-47.
• Nurieva, RI, Chung Y, Hwang D, Yang XO, Kang HS, Ma L, Wang Y-H, Watowich SS, Jetten AM, Tian Q, Dong C. Generation of follicular helper T cells is mediated by IL-21 but independent of TH1, TH2 or TH17 lineages. Immunity. 2008, 29:138-149.
• Pappu BP, Borodovsky A, Zheng TS, Yang X, Wu P, Dong X, Weng S, Browning B, Scott ML, Ma L, Su L, Tian Q, Schneider P, Flavell RA, Dong C*, Burkly LC. TL1A-DR3 interaction regulates Th17 cell function and Th17-mediated autoimmune disease. J Exp Med. 2008, 205(5): 1049-62. (* co-correspondent authors)
• Yamazaki T, Yang XO, Chung Y, Fukunaga A, Nurieva R, Pappu B, Martin-Orozco N, Kang HS, Ma L, Panopoulos AD, Craig S, Watowich SS, Jetten AM, Tian Q, Dong C. CCR6 regulates the migration of inflammatory and regulatory T cells. J Immunol. 2008, 181(12):8391-401.
• Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z, Dong C. Regulation of inflammatory responses by IL-17F. J Exp Med. 2008,  205(5): 1063-75.
• Yang XO, Nurieva R, Martinez GJ, Kang HS, Chung Y, Pappu BP, Shah B, Chang SH, Schluns KS, Watowich SS, Feng XH, Jetten AM, Dong C. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity. 2008, 29(1): 44-56.
• Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, Watowich SS, Tian Q, Jetten AM, Dong C. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity. 2008,  28(1): 29-39.
• Chang M, Lee AJ, Fitzpatrick L, Zhang M, Sun SC. NF-kappa B1 p105 regulates T cell homeostasis and prevents chronic inflammation. J Immunol 2009, 182(5): 3131-8.
• Jin W, Zhou XF, Yu J, Cheng X, Sun SC. Regulation of Th17 cell differentiation and EAE induction by MAP3K NIK. Blood 2009, 113(26): 6603-10.
• Li D, Molldrem JJ, Ma Q. LFA-1 Regulates CD8+ T Cell Activation via T Cell Receptor-mediated and LFA-1-mediated Erk1/2 Signal Pathways. J Biol Chem 2009, 284(31): 21001-10.
• Li Y, Thapa P, Hawke D, Kondo Y, Furukawa K, Furukawa K, Hsu FF, Adlercreutz D, Weadge J, Palcic MM, Wang PG, Levery SB, Zhou D. Immunologic Glycosphingolipidomics and NKT Cell Development in Mouse Thymus. J Proteome Res 2009, 8(6): 2740-51.
• Ma LJ, Acero LF, Zal T, Schluns KS. Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8alphaalpha IELs. J Immunol 2009, 183(2): 1044-54.
• Martin-Orozco N, Chung Y, Chang SH, Wang YH, Dong C. Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells. Eur J Immunol 2009, 39(1): 216-24.
• Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, Matskevitch TD, Wang YH, Dong C. Bcl6 Mediates the Development of T Follicular Helper Cells. Science 2009, 325:1001-1005.
• Voo KS, Wang YH, Santori FR, Boggiano C, Wang YH, Arima K, Bover L, Hanabuchi S, Khalili J, Marinova E, Zheng B, Littman DR, Liu YJ. Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci U S A 2009, 106(12): 4793-8.
• Yang XO, Angkasekwinai P, Zhu J, Peng J, Liu Z, Nurieva R, Liu X, Chung Y, Chang SH, Sun B, Dong C. Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment. Nat Immunol 2009, 10(12): 1260-1267.
• Kim TK, Billard MJ, Wieder ED, McIntyre BW, Komanduri KV. Co-engagement of alpha(4)beta(1) integrin (VLA-4) and CD4 or CD8 is necessary to induce maximal Erk1/2 phosphorylation and cytokine production in human T cells. Hum Immunol. 2010, 71(1): 23-8.

Research Theme 4: UV-Induced Immunosuppression and Skin Cancer

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Objective: Understand the cellular and molecular mechanisms by which UV radiation causes immunosuppression and skin cancer

Relevant Publications

• Walterscheid JP, Ullrich SE, Nghiem DX. Platelet-activating factor, a molecular sensor for cellular damage, activates systemic immune suppression. J Exp Med. 2002, 195(2): 171-9.
• Walterscheid JP, Nghiem DX, Kazimi N, Nutt LK, McConkey DJ, Norval M, Ullrich SE. Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor. Proc Natl Acad Sci U S A. 2006, 103(46): 17420-5.
• Sreevidya CS, Khaskhely NM, Fukunaga A, Khaskina P, Ullrich SE. Inhibition of photocarcinogenesis by platelet-activating factor or serotonin receptor antagonists. Cancer Res. 2008, 68(10): 3978-84.
• Limón-Flores AY, Chacón-Salinas R, Ramos G, Ullrich SE. Mast Cells Mediate the Immune Suppression Induced by Dermal Exposure to JP-8 jet fue1. Toxicol Sci. 2009, 112(1): 144-52.
• Ramos G, Limon-Flores AY, Ullrich SE. JP-8 induces immune suppression via a reactive oxygen species NF-kappabeta-dependent mechanism. Toxicol Sci 2009, 108(1): 100-9.

Research Theme 5: Immunotherapy of Leukemia and Lymphoma

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Objective: Develop more effective immunotherapy for human leukemia, lymphoma and multiple myeloma

Relevant Publications

• Molldrem JJ, Lee PP, Kant S, Wieder E, Jiang W, Lu S, Wang C, Davis MM. Chronic myelogenous leukemia shapes host immunity by selective deletion of high-avidity leukemia-specific T cells. J Clin Invest. 2003, 111(5): 639-47.
• Molldrem JJ. Vaccinating transplant recipients. Nat Med. 2005, 11(11): 1162-3.
• Neelapu SS, Kwak LW, Kobrin CB, Reynolds CW, Janik JE, Dunleavy K, White T, Harvey L, Pennington R, Stetler-Stevenson M, Jaffe ES, Steinberg SM, Gress R, Hakim F, Wilson WH. Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma. Nat Med. 2005, 11(9): 986-91.
• Kowolik CM, Topp MS, Gonzalez S, Pfeiffer T, Olivares S, Gonzalez N, Smith DD, Forman SJ, Jensen MC, Cooper LJ. CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Res. 2006, 66(22): 10995-1004.
• Yang J, Qian J, Wezeman M, Wang S, Lin P, Wang M, Yaccoby S, Kwak LW, Barlogie B, Yi Q. Targeting beta2-microglobulin for induction of tumor apoptosis in human hematological malignancies. Cancer Cell. 2006, 10(4): 295-307.
• Chung, Y. S., Qin, H., Kang, C.-Y., Kim, S., Kwak, L. W., and Dong, C. An NKT cell-mediated autologous vaccine generates potent CD4+ T-cell-dependent anti-lymphoma immunity. 2007, Blood. 110: 2013-2019.
• Singh H, Manuri PR, Olivares S, Dara N, Dawson MJ, Huls H, Hackett PB, Kohn DB, Shpall EJ, Champlin RE, Cooper LJ. Redirecting specificity of T-cell populations for CD19 using the Sleeping Beauty system. Cancer Res. 2008, 68(8): 2961-71.
• Dossett ML, Teague RM, Schmitt TM, Tan X, Cooper LJ, Pinzon C, Greenberg PD. Adoptive immunotherapy of disseminated leukemia with TCR-transduced, CD8+ T cells expressing a known endogenous TCR. Mol Ther. 2009, 17(4): 742-9.
• Qian J, Hong S, Wang S, Zhang L, Sun L, Wang M, Yang J, Kwak LW, Hou J, Yi Q. Myeloma cell line-derived, pooled heat shock proteins as a universal vaccine for immunotherapy of multiple myeloma. Blood. 2009, 114(18): 3880-9.
• Qin H, Cha SC, Neelapu SS, Lou Y, Wei J, Liu YJ, Kwak LW. Vaccine site inflammation potentiates idiotype DNA vaccine-induced therapeutic T cell-, and not B cell-, dependent antilymphoma immunity. Blood. 2009, 114(19): 4142-9.
• Voorhees PM, Chen Q, Small GW, Kuhn DJ, Hunsucker SA, Nemeth JA, Orlowski RZ. Targeted inhibition of interleukin-6 with CNTO 328 sensitizes pre-clinical models of multiple myeloma to dexamethasone-mediated cell death. Br J Haematol. 2009, 145(4): 481-90.
• Wang M, Sun L, Qian J, Han X, Zhang L, Lin P, Cai Z, Yi Q. Cyclin D1 as a universally expressed mantle cell lymphoma-associated tumor antigen for immunotherapy. Leukemia. 2009, 23(7): 1320-8.
• Wang Y, Li D, Jones D, Bassett R, Sale GE, Khalili J, Komanduri KV, Couriel DR, Champlin RE, Molldrem JJ, Ma Q. Blocking LFA-1 activation with lovastatin prevents graft-versus-host disease in mouse bone marrow transplantation. Biol Blood Marrow Transplant. 2009, 5(12): 1513-22.
• Yang J, Cao Y, Hong S, Li H, Qian J, Kwak LW, Yi Q. Human-like mouse models for testing the efficacy and safety of anti-beta2-microglobulin monoclonal antibodies to treat myeloma. Clin Cancer Res. 2009, 15(3): 951-9.
• Zheng Y, Cai Z, Wang S, Zhang X, Qian J, Hong S, Li H, Wang M, Yang J, Yi Q. Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis. Blood. 2009, 114(17): 3625-8.

Research Theme 6: Immunotherapy of Solid Tumors

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Objective: Enhance antitumor immune responses by strengthening effector T-cell responses against cancer and blocking the immunosuppressive mechanisms within the tumor microenvironment

Relevant Publications

• Kershaw MH, Westwood JA, Hwu P. Dual-specific T cells combine proliferation and antitumor activity. Nat Biotechnol. 2002, 20(12): 1221-7.
• Overwijk W, Theoret MR, Finkelstein SE, Surman DR, de Jong LA, Vyth-Dreese FA, Dellemijn TA, Antony PA, Spiess PJ, Palmer DC, Heimann DM, Klebanoff CA, Yu Z, Hwang LN, Feigenbaum L, Kruisbeek AM, Rosenberg SA, Restifo NP. Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells. J Exp Med. 2003, 198(4): 569-80.
• Wang G, Tschoi M, Spolski R, Lou Y, Ozaki K, Feng C, Kim G, Leonard WJ, Hwu P. In vivo antitumor activity of interleukin 21 mediated by natural killer cells. Cancer Res. 2003, 63(24): 9016-22.
• Lou Y, Wang G, Lizée G, Kim GJ, Finkelstein SE, Feng C, Restifo NP, Hwu P. Dendritic cells strongly boost the antitumor activity of adoptively transferred T cells in vivo. Cancer Res. 2004,  64(18): 6783-90.
• Overwijk W, de Visser KE, Tirion FH, de Jong LA, Pols TW, van der Velden YU, van den Boorn JG, Keller AM, Buurman WA, Theoret MR, Blom B, Restifo NP, Kruisbeek AM, Kastelein RA, Haanen JB. Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant. J Immunol. 2006,  176(9): 5213-22.
• Liu S, Lizée G, Lou Y, Liu C, Overwijk W, Wang G, Hwu P. IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells. Int Immunol. 2007, 19(10): 1213-21.
• Lou Y, Liu C, Kim GJ, Liu YJ, Hwu P, Wang G. Plasmacytoid dendritic cells synergize with myeloid dendritic cells in the induction of antigen-specific antitumor immune responses. J Immunol. 2007, 178(3): 1534-41.
• Murphy A, Westwood JA, Brown LE, Teng MW, Moeller M, Xu Y, Smyth MJ, Hwu P, Darcy PK, Kershaw MH. Antitumor activity of dual-specific T cells and influenza virus. Cancer Gene Ther. 2007, 14(5): 499-508.
• Abad JD, Wrzensinski C, Overwijk W, De Witte MA, Jorritsma A, Hsu C, Gattinoni L, Cohen CJ, Paulos CM, Palmer DC, Haanen JB, Schumacher TN, Rosenberg SA, Restifo NP, Morgan RA.T-cell receptor gene therapy of established tumors in a murine melanoma model. J Immunother. 2008, 31(1): 1-6.
• Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, Hwu P, Restifo NP, Overwijk WW, Dong C. T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity. 2009, 31(5): 787-98.
• Sikora AG, Jaffarzad N, Hailemichael Y, Gelbard A, Stonier SW, Schluns KS, Frasca L, Lou Y, Liu C, Andersson HA, Hwu P, Overwijk WW. IFN-alpha enhances peptide vaccine-induced CD8+ T cell numbers, effector function, and antitumor activity. J Immunol. 2009, 182(12): 7398-407.
• Thapa P, Zhang G, Xia C, Gelbard A, Overwijk WW, Liu C, Hwu P, Chang DZ, Courtney A, Sastry JK, Wang PG, Li C, Zhou D. Nanoparticle formulated alpha-galactosylceramide activates NKT cells without inducing anergy. Vaccine 2009, 27(25-26): 3484-8.