Abstract
Although the immunological- and cytokine-mediated events preceding the development of full-blown Type 1 diabetes in the nonobese diabetic (NOD) mouse model are becoming better known, the events preceding disease in humans are less well-characterized. In human Type 1 diabetes, much effort has focused on establishing criteria for disease-development risk, which include genetic associations and the presence of autoantibodies. The contribution of human leukocyte antigen (HLA) alleles for susceptibility (HLA-DR3, HLA-DR4) or resistance (HLA-DQ8) to disease have been studied (reviewed in refs. 1–4). The diagnostic use of autoantibodies titers to isleT cell antigens such as glutamic acid decarboxylase (GAD) 65, insulin, and other antigens provide a risk assessment for disease onset (5). These markers, along with metabolic measurements, allow clinicians to track patients who are likely to develop disease and to provide support when disease development is imminent.
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References
She, J.-X. (1996) Susceptibility to type I diabetes:HLA-DQ and DR revisited. Immunol. Today 17, 323–329.
Todd, J. A. (1999) From gemone to aetiology in a multifactorial disease, type 1 diabetes. BioEssays 21, 164–174.
Atkinson, M. A. and Maclaren, N. K. (1994) The pathogenesis of insulin-dependent diabetes mellitus. N. Eng. J. Med. 331, 1428–1436.
Lernmark, A. (1999) Selected culprits in type 1 diabetes β-cell killing. J. Clin. Invest. 104, 1487–1489.
Verge, C. F., Gianani, R., Kawasaki, E., Yu, L., Pietropaolo, M., Jackson, R. A., et al. (1996) Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes 45, 926–933.
Charlton, B. and Lafferty, K. J. (1995) The Th1/Th2 balance in autoimmunity. Curr. Opin. Immunol. 7, 793–798.
Liblau, R. S., Singer, S. M., and McDevitt, H. O. (1995) Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol. Today 16, 34–38.
Rabinovitch, A. (1998) An update on cytokines in the pathogenesis of insulin-dependent diabetes mellitus. Diabetes Metabol. Rev. 14, 129–151.
Mandrup-Poulsen, T. (1996) The role of interleukin-1 in the pathogenesis of IDDM. Diabetology 39, 1005–1029.
Foulis, A. K., Farquharson, M. A., and Meager, A. (1987) Immunoreactive alpha-interferon in insulin-secreting beat cells in type 1 diabetes mellitus. Lancet ii, 1423–1427.
Huang, X., Yuan, J., Goddard, A., Foulis, A., James, R. F. L., Lernmark, A., et al. (1995) Interferon expression in the pancreases of patients with type 1 diabetes. Diabetes 44, 658–664.
Amrani, A., Verdaguer, J., Thiessen, S., Bou, S., and Santamaria, P. (2000) IL-1α, IL-1β, and IFN-γ mark B cells for Fas-dependent destruction by diabetogenic CD4+ T lymphcytes. J. Clin. Invest. 105, 459–468.
Rabinovitch, A. and Suarez-Pinzon, W. L. (1998) Cytokines and their roles in pancreatic islet β-cell destruction and insulin-dependent diabetes mellitus. Biochem. Pharmacol. 55, 1139–1149.
Seino, H., Takahashi, K., Satoh, J., Zhu, X. P., Sagara, M., Masuda, T., et al. (1993) Prevention of autoimmune diabetes with lymphotoxin in NOD mice. Diabetes 42, 398–404.
Satoh, J., Seino, H., Shintani, S., Tanaka, S.-I., Ohteki, T., Masada, T., et al. (1990) Inhibition of type 1 diabetes in BB rats with recombinant human tumour necrosis factor-α. J. Immunol. 145, 1395–1399.
Zielasek, J., Burkart, V., Naylor, P., Goldstein, A., Kiesel, U., and Kolb, H. (1990) Interleukin 2-dependent control of disease development in spontaneously diabetic BB rats. Immunology 69, 209–214.
Jacob, C. O., Asiso, S., Michie, S. A., McDevitt, H. O., and Acha-Orbea, H. (1990) Prevention of diabetes in nonobese diabetic mice by tumour necrosis factor (TNF): similarities between TNFα and IL-1. Proc. Natl. Acad. Sci. USA 87, 968–972.
Netea, M. G., Hancu, N., Blok, W. L., Grigorescu-Sido, P., Popa, L., Popa, V., and van der Meer, J. W. (1997) Interleukin 1 beta, tumour necrosis factor-alpha and interleukin 1 receptor antagonist in newly diagnosed insulin-dependent diabetes mellitus: comparison to long standing diabetes and healthy individuals. Cytokine 9, 284–287.
Hussain, M. J., Peakman, M., Gallati, H., Lo, S. S. S., Hawa, M., Viberti, G. C., et al. (1996) Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM. Diabetology 39, 60–69.
Walker, R., Bone, A. J., Cooke, A., and Baird, D. J. (1988) Distinct macrophage subpopulations in pancreas of prediabetic BB/E rats: possible role for macrophages in the pathogenesis of IDDM. Diabetes 37, 1301–1304.
Espersen, G. T., Mathiesen, O., Grunnet, N., and Jensen, S. D. (1993) Cytokine plasma levels and lymphocyte subsets in patients with newly diagnosed insulin-dependent (type 1) diabetes mellitus before and following initial insulin treatment. APMIS 101, 703–706.
Cavallo, M. G., Pozzilli, P., Bird, C., Wadhwa, M., Meager, A., Visalli, N., et al. (1991) Cytokines in the sera from insulin-dependent diabetic patients at diagnosis. Clin. Exp. Immunol. 86, 256–259.
Lorini, R., De Amici, M., d’Annunzio, G., Vitali, L., and Scaramuzza, A. (1995) Low serum levels of tumor necrosis factor-alpha in insulin-dependent diabetic children. Hormone Res. 43, 206–209.
Mooradian, A. D., Reed, R. L., Meredith, K. E., and Scuderi, P. (1991) Serum level of tumor necrosis factor and IL-1α and IL-1β in diabetic patients. Diabetes Care 14, 63–65.
Tovo, P. A., Cerutti, F., Palomba, E., Salomone, C., and Pugliese, A. (1984) Evidence of circulating interferon-gamma in newly diagnosed diabetic children. Acta Paed. Scand. 73, 785–788.
Ng, W. Y., Thai, A. C., Lui, K. F., Yeo, P. P. B., and Cheah, J. S. (1999) Systemic levels of cytokines and GAD-specific autoantibody isotypes in Chinese IDDM patients. Diabetes Res. Clin. Practice 43, 127–135.
Wilson, S. B., Kent, S. C., Patton, K. T., Orban, T., Jackson, R. A., Exley, M., et al. (1998) Extreme Th1 bias of invariant Vα24JαQ T cells in type 1 diabetes. Nature 391, 177–181.
Redondo, M. J., Gottlieb, P. A., Motheral, T., Mulgrew, C., Rewers, M., Babu, S., et al. (1999) Heterophile anti-mouse immunoglobulin may interfer with cytokine measurements in patients with HLA alleles protective for type 1A diabetes. Diabetes 48, 2166–2170.
She, J.-X., Ellis, T. M., Wilson, S. B., Wasserfall, C. H., Marron, M., Reimsneider, S., et al. (1999) Heterophile antibodies segregate in families and are associated with protection from type 1 diabetes. Proc. Natl. Acad. Sci. USA 96, 8116–8119.
Boscato, L. M. and Stuart, M. C. (1986) Incidence and specificity of interference in two-site immunoassays. Clin. Chem. 32, 1491–1495.
Boscato, L. M. and Stuart, M. C. (1988) Heterophilic antibodies: a problem for all immunoassays. Clin. Chem. 34, 27–33.
Levinson, S. S. (1992) Antibody multispecificity in immunoassay interference. Clin. Biochem. 25, 77–87.
Orban, T., Kent, S. C., Malik, P., Milner, J. D., Schuster, K., Jackson, R. A., et al. (2001) Heterophile antibodies indicate progression of autoimmunity in human type 1 diabetes mellitus before clinical onset. Autoimmunity, in press.
Nikoskelainen, J. and Hanninen, P. (1975) Antibody response to Epstein-Barr virus in infectious mononucleosis. Infect. Immunity 11, 42–51.
Clofent-Sanchez, G., Laroche-Traiean, J., Lucas, S., Rispal, P., Pellegrin, J. L., Nurden, P., et al. (1997) Incidence of anti-mouse antibodies in thrombocytopenic patients with autoimmune disorders. Human Antibodies 8, 50–59.
Carson, D. A., Chen, P. P., Fox, R. I., Kipps, T. J., Jirik, F., Goldfien, R. D., et al. (1987) Rheumatoid factor and immune networks. Ann. Rev. Immunol. 5, 109–126.
Trotter, J. L., Damico, C. A., Trotter, A. L., Collins, K. G., and Cross, A. H. (1995) Interleukin-2 binding proteins in sera from normal subjects and multiple sclerosis patients. Neurology 45, 1971–1974.
Senaldi, G., Peakman, M., Natoli, C., Hussain, M. J., Gallati, H., McManus, T., et al. (1994) Relationship between the tumour-associated antigen 90K and cytokines in the circulation of persons infected with human immunodeficiency virus. J. Infect. 28, 31–39.
Ohshima, Y., Katamura, K., Miura, M., Mikawa, H., and Mayumi, M. (1995) Serum levels of interleukin 4 and soluble CD23 in children with allergic disorder. Eur. J. Paed. 154, 723–728.
Abbas, A. K., Murphy, K. M., and Sher, A. (1996) Functional diversity of helper T lymphocytes. Nature 383, 787–793.
Coffman, R. L., Lebman, D. A., and Rothman, P. (1993) Mechanism and regulation of immunolglobulin isotype switching. Adv. Immunol. 54, 229–270.
Petersen, J. S., Kulmala, P., Clausen, J. T., Knip, M., Dyrberg, T., and the Childhood Diabetes in Finland Study Group. (1999) Progression to type 1 diabetes is associated with a change in the immunolglobulin isotype profile of autoantibodies to glutamic acid decarboxylase (GAD65). Clin. Immunol. 90, 276–281.
Bonifacio, E., Scirpoli, M., Kredel, K., Fuchtenbusch, M., and Ziegler, A.-G. (1999) Early autoantibody responses in prediabetics are IgG1 dominated and suggest antigen specific regulation. J. Immunol. 163, 525–532.
Harrison, L. C., Honeyman, M. C., DeAizpurua, H. J., Schmidli, R. S., Colman, P. G., Tait, B. D., et al. (1993) Inverse relation between humoral and cellular immunity glutamic acid decarboxylase in subjects at risk of insulin-dependent diabetes. Lancet 341, 1365–1369.
Gepts, W. (1965) Pathological anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14, 619–633.
Atkinson, M. A. and Maclaren, N. K. (1993) Islet cell autoantigens in insulin-dependent diabetes. J. Clin. Invest. 92, 1608–1616.
Bottazzo, G. F., Dean, B. M., McNally, J. M., MacKay, E. H., Swift, P. G. F., and Gamble, D. R. (1985) In situ characterization of autoimmune phenoma and expression of HLA molecules in the pancreas in diabetic insulitis. N. Engl. J. Med. 313, 353–360.
Foulis, A. K., McGill, M., and Farquharson, M. A. (1991) Insulitis in type 1 (insulin-dependent) diabetes mellitus in man-macrophages, lymphocytes, and interferon-γ containing cells. J. Pathol. 165, 97–103.
Hanninen, A., Jalkanen, S., Salmi, M., Toikkannen, S., Nikolakaros, G., and Simell, O. (1992) Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset insulin-dependent diabetes mellitus. J. Clin. Invest. 90, 1901–1910.
Santamaria, P., Lewis, C., Jessurun, J., Sutherland, D. E. R., and Barbosa, J. J. (1994) Skewed T cell receptor usage junctional and heterogeneity among isletitis αβ and γδ T cells in human IDDM. Diabetes 43, 599–606.
Conrad, B., Weidmann, E., Trucco, G., Rudert, W. A., Behboo, R., Ricordi, C., et al. (1994) Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology. Nature 371, 351–355.
Roep, B. O. (1996) T cell responses to autoantigens in IDDM. Diabetes 45, 1147–1156.
Peakman, M., Stevens, E. J., Lohmann, T., Narendran, P., Dromey, J., Alexander, A., et al. (1999) Naturally processed and presented epitopes of the islet cell autoantigen IA-2 eluted from HLA-DR4. J. Clin. Invest. 104, 1449–1451.
Abulafia-Lapid, R., Elias, D., Raz, I., Keren-Zur, Y., Atlan, H., and Cohen, I. R. (1999) T cell proliferative responses of type 1 diabetes patients and healthy individuals to human hsp60 and its peptides. J. Autoimmunol. 12, 121–129.
Cohen, I. R. (1997) The Th1/Th2 dichotomy, hsp60 autoimmunity, and type 1 diabetes. Clin. Immunol. Immunopath. 84, 103–106.
Buschard, K., Schloot, N. C., Kaas, A., Bock, T., Horn, T., Fredman, P., and Roep, B. O. (1999) Inhibition of insulin-specific autoreactive T cells by sulphatide which is variably expressed in beta cells. Diabetology 42, 1212–1218.
Atkinson, M. A., Bowman, M. A., Campbell, L., Darrow, B. L., Kaufman, D. L., and Maclaren, N. K. (1994) Cellular immunity to a determinant common to glutamate decarboxylase and Coxsackie virus in insulin-dependent diabetes. J. Clin. Invest. 94, 2125–2129.
Naquet, P., Ellis, J., Tibensky, D., Kenshole, A., Singh, B., Hodges, R., et al. (1988) T cell autoreactivtiy to insulin in diabetic and related non-diabetic individuals. J. Immunol. 140, 2569–2578.
Semana, G., Gausling, R., Jackson, R. A., and Hafler, D. A. (1999) T cell autoreactivity to proinsulin epitopes in diabetic patients and healthy subjects. J. Autoimmunol. 12, 259–267.
Congia, M., Patel, S., Cope, A. P., De Virgilis, S., and Sonderstrup, G. (1998) T cell epitopes of insulin defined in HLA-DR4 transgenic mice are derived from preproinsulin and proinsulin. Proc. Natl. Acad. Sci. USA 95, 3883–3888.
Rudy, G., Stone, N., Harrison, L. C., Colman, P. G., McNair, P., Brusic, V., et al. (1995) Similar peptides from tewo beta cell autoantigens, proinsulin and glutamic acid decarboxylase, stimulate T cells of individuals at risk for insulin-dependent diabetes. Mol. Med. 1, 625–633.
Endl, J., Otto, H., Jung, G., Dreisbusch, B., Donie, F., Stahl, P., et al. (1997) Identification of naturally processed T cell epitopes from glutamic acid decarboxylase presented in the context of HLA-DR alleles by T lymphocytes of recent onset IDDM patients. J. Clin. Invest. 99, 2405–2415.
Herman, A. E., Tisch, R. M., Patel, S. D., Parry, S. L., Olson, J., Noble, J. A., et al. (1999) Determination of glutamic acid decarboxylase 65 peptides presented by the type 1 diabetes-associated HLA-DQ8 class II molecule identifies an immunogenic peptide motif. J. Immunol. 163, 6275–6282.
Harfouch-Hammond, E., Walk, T., Otto, H., Jung, G., Bach, J. F., van Endert, P. M., et al. (1999) Identification of peptides from autoantigens GAD65 and IA-2 that bind to HLA class II molecules predisposing to or protecting from type 1 diabetes. Diabetes 48, 1937–1947.
Durinovic-Bello, I., Hummel, M., and Ziegler, A.-G. (1996) Cellular immune response to diverse islet cell antigens in IDDM. Diabetes 45, 795–800.
Mayer, A., Rharbaoui, F., Thivolet, C., Orgiazzi, J., and Madec, A. M. (1999) The relationship between peripheral T cell reactivity to insulin, clinical remissions and cytokine production in type 1 (insulin-dependnt) diabetes mellitus. J. Clin. Endocrin. Metabol. 84, 2419–2424.
Ellis, T. M., Schatz, D. A., Ottendorfer, E. W., Lan, M. S., Wasserfall, C., Salisbury, P. J., et al. (1998) The relationship between humoral and cellular immunity to IA-2 in IDDM. Diabetes 47, 566–569.
Schloot, N. C., Roep, B. O., Wegmann, D. R., Yu, L., Wang, T. B., and Eisenbarth, G. S. (1997) T cell reactivity to GAD65 peptide sequences shared with Coxsackie virus protein in recent-onset IDDM, post-onset IDDM patients and control subjects. Diabetology 40, 332–338.
Ellis, T. M., Jodoin, E., Ottendorfer, E., Salisbury, P, She, J. X., Schatz, D. A., et al. (1999) Cellular immune responses against proinsulin: no evidence for enhanced reactivity in individuals with IDDM. Diabetes 48, 299–303.
Schloot, N. C., Roep, R. O., Wegmann, D., Yu, L., Chase, H. P., Wang, T., and Eisenbarth, G. S. (1997) Altered immune response to insulin in newly diagnosed compared to insulin-treated diabetic patients and healthy control subjects. Diabetology 40, 562–572.
Roep, B. O., Atkinson, M. A., van Endert, P. M., Gottlieb, P. A., Wilson, S. B., and Sachs, J. A. (1999) Autoreactive T cell responses in insulin-dependent (type 1) diabetes mellitus. J. Autoimmun. 13, 267–282.
Zhang, J., Markovic-Plese, S., Lacet, B., Raus, J., Weiner, H. L., and Hafler, D. A. (1994) Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and protolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J. Exp. Med. 179, 973–984.
Karlsson, M. G. and Ludvigsson, J. (1998) Determination of mRNA expression for IFN-gamma and IL-4 in lymphocytes from children with IDDM by RT-PCR technique. Diabetes Res. Clin. Practice 40, 21–30.
Kallman, B. A., Lampeter, E. F., Hanifi-Moghaddam, P., Hawa, M., Leslie, R. D., and Kolb, H. (1999) Cytokine secretion patterns in twins discordant for type 1 diabetes. Diabetology 42, 1080–1085.
Rapoport, M. J., Mor, A., Vardi, P., Ramot, Y., Winker, R., Hindi, A., and Bistritzer, T. (1998) Decreased secretion of Th2 cytokines precedes up-regulated and delayed secretion of Th1 cytokines in activated peripheral blood mononuclear cells from patients with insulin-dependent diabetes mellitus. J. Autoimmun. 11, 635–642.
Berman, M. A., Sandborg, C. I., Wang, Z., Imfeld, K. L., Zaldivar Jr., F., Dadufalza, V., and Buckingham, B. A. (1996) Decreased IL-4 production in new onset type 1 insulin-dependent diabetes mellitus. J. Immunol. 157, 4690–4696.
Kaye, W. A., Adri, M. N., Soeldner, J. S., Rabinowe, S. L., Kaldany, A., Kahn, C. R., et al. (1986) Acquired defect in interleukin-2 production in patients with type 1 diabetes mellitus. N. Engl. J. Med. 315, 920–924.
Dosch, H.-M., Cheung, R. K, Karges, W., Pietropaolo, M., and Becker, D. J. (1999) Persistent T cell anergy in human type 1 diabetes. J. Immunol. 163, 6933–6940.
Miyazaki, I., Cheung, R. K., Gaedigk, R., Hui, M. F., Van der Meulin, J., Rajotte, R. V., et al. (1995) T cell activation and anergy to islet cell antigen in type 1 diabetes. J. Immunol. 154, 1461–1469.
Nervi, S., Atlan-Gepner, C., Fossat, C., and Vialettes, B. (1999) Constitutive impaired TCR/CD3-mediated activation of T cells in IDDM patients co-exist with normal costimulation pathways. J. Autoimmun. 13, 247–255.
Bendelac, A., Rivera, M. N., Park, H.-S., and Roark, J. H. (1997) Mouse CD1-specific NK1 T cells: development, specificity, and function. Ann. Rev. Immunol. 15, 535–562.
Bendelac, A., Lantz, O., Quimby, M. E., Yewdell, J. W., Bennink, J. R., and Brutkiewicz, R. R. (1995) CD1 recognition by mouse NK1+ T lymphocytes. Science 268, 863–865.
Tamada, K., Harada, M., Abe, K., Li, T., Tada, H., Onoe, Y., et al. (1997) Immunosuppressive activity of cloned natural killer (NK1.1+) T cells established from murine tumor-infiltrating lymphocytes. J. Immunol. 158, 4846–4854.
Yoshimoto, T. and Paul, W. (1994) CD4+NK1.1+ T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD-3. J. Exp. Med. 179, 1285–1295.
Yoshimoto, T., Bendelac, A., Watson, C., Hu-Li, J., and Paul, W. E. (1995) Role of NK1.1+ T cells in a Th2 response and in immunoglobulin E production. Science 270, 1845–1847.
Brown, D. R., Fowell, D. J., Corry, D. B., Wynn, T. A., Moskowitz, N. H., Cheever, A. W., et al. (1996) β2-microglobulin-dependent NK1.1+T cells are not essential for T helper cell 2 immune responses. J. Exp. Med. 184, 1295–1304.
Smiley, S. T., Kaplan, M. H., and Grusby, M. J. (1997) Immunoglobulin E production in the absence of interleukin-4-secreting CD1-dependent cells. Science 275, 977–979.
Mendiratta, S. K., Martin, W. D., Hong, S., Boesteanu, A., Joyce, S., and Van Kaer, L. (1997) CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4. Immunity 6, 469–477.
Chen, Y.-H., Chiu, N. M., Mandai, M., Wang, N., and Wang, C.-R. (1997) Impaired NK1+ T cell development and early IL-4 production in CD1-deficient mice. Immunity 6, 459–467.
Porcelli, S., Yockey, C. E., Brenner, M. B., and Balk, S. P. (1993) Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8-α/β T cells demonstrates preferential use of several Vβ genes and an invariant TCR α chain. J. Exp. Med. 178, 1–16.
Porcelli, S., Gerdes, D., Fertig, A., and Balk, S. (1996) Human T cells expressing an invariant Vα24JαQ TCRα are CD4-negative and heterogeneous with respect to TCRβ expression. Human Immunol. 48, 63–67.
Masuda, K., Makino, Y., Cui, J., Ito, T., Tokuhisa, T., Takahama, Y., et al. (1997) Phenotypes and invariant αβ TCR expression of peripheral Vα14+ NK T cells. J. Immunol. 158, 2076–2082.
Joyce, S., Woods, A. S., Yewdell, J. W., Bennink, J. R., De Silva, A. D., Boesteanu, A., et al. (1998) Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol. Science 279, 1541–1544.
Kawano, T., Cui, J., Koezuka, Y., Toura, I., Kaneko, Y., Motoki, K., et al. (1997) CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides. Science 278, 1626–1629.
Brossay, L., Chioda, M., Burdin, N., Koezuka, Y., Casorati, G., Dellabona, P., et al. (1998) CD1d-mediated recognition of an a-Galactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J. Exp. Med. 188, 1521–1528.
Spada, F. M., Koezuka, Y., and Porcelli, S. A. (1998) CD1d-restricted recognition of synthetic glycolipid antigens by human killer T cells. J. Exp. Med. 188, 1529–1534.
Zeng, Z.-H., Castano, A. R., Segelke, B. W., Stura, E. A., Peterson, P. A., and Wilson, I. A. (1997) Crystal structure of mouse CD1: MHC-like fold with a large hydrophobic binding groove. Science 277, 339–345.
Gumperz, J. E., Roy, C., Makowska, A., Lum, D., Sugita, M., Podrebarac, T., et al. (2000) Murine CD1d-restricted T cell recogition of cellular lipids. Immunity 12, 211–221.
Chen, H. and Paul, W. (1997) Cultured NK1.1+CD4+ T cells produce large amounts of IL-4 and IFN-γ upon activation by anti-CD3 or CD1. J. Immunol. 159, 2240–2249.
Bendelac, A. (1995) CD1: presenting unusual antigens to unusual T lymphocytes. Science 269, 185,186.
Behar, S. M., Podrebarac, T. A., Roy, C. J., Wang, C. R., and Brenner, M. B. (1999) Diverse TCRs recognize murine CD1. J. Immunol. 162, 161–167.
Cardell, S., Tangri, S., Chan, S., Kronenberg, M., Benoist, C., and Mathis, D. (1995) CD1-restricted CD4+ T cells in major histocompatibility complex class II-deficient mice. J. Exp. Med. 182, 993–1004.
Chiu, Y.-H., Jayawardena, J., Weiss, A., Lee, D., Park, S.-H., Varsat-Dautry, A., and Bendelac, A. (1999) Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments. J. Exp. Med. 189, 103–110.
Exley, M., Garcia, J., Balk, S. P., and Porcelli, S. (1997) Requirements for CD1d recognition by human invariant Vα24JαQ+ NKR-P1A+ T cells. J. Exp. Med. 186, 109–120.
Davodeau, F., Peyrat, M.-A., Necker, A., Dominici, R., Blanchard, F., et al. (1997) Close phenotypic and functional similarities between human and murine αβ T cells expressing invariant TCR-α chains. J. Immunol. 158, 5603–5611.
Kent, S. C., Hafler, D. A., Strominger, J. L., and Wilson, S. B. (1999) Noncanonical Vα24JαQ T cells with conservative a chain CDR3 region amino acid substitutions are restricted by CD1d. Human Immunol. 60, 1080–1089.
Park, S. H., Roark, J. H., and Bendelac, A. 1998. Tissue-specific recognition of mouse CD1 molecules. J. Immunol. 160, 3128–3134.
Garboczi, D. N., Ghosh, P., Utz, U., Fan, Q. R., Biddison, W. E., and Wiley, D. C. (1996) Structure of the complex between human T cell receptor, viral peptide and HLA-A2. Nature 384, 134–141.
Balk, S. P., Ebert, E. C., Blumenthal, R. L., McDermott, F. V., Wucherfennig, K. W., Landau, S. B., et al. (1991) Oligoclonal expansion and CD1 recognition by human intestinal intraepithelial lymphocytes. Science 253, 1411–1415.
Blumberg, R. S., Terhorst, C., Bleicher, P., McDermott, F. V., Allan, C. H., Landau, S. B., et al. (1991) Expression of a nonpolymorphic MHC classI-like molecule, CD1D, by human intestinal epithelial cells. J. Immunol. 147, 2518–2524.
Cui, J., Shin, T., Kawano, T., Sato, H., Kondo, E., Toura, I., et al. (1997) Requirement for Vα14 NKT cells in IL-12-mediated rejection of tumors. Science 278, 1623–1626.
Nakamura, E., Kubota, H., Sato, M., Sugie, T., Yoshida, O., and Minato, N. (1997) Involvement of NK1+ CD4−CD8−αβ T cells and endogenous IL-4 in non-MHC-restricted rejection of embryonal carcinoma in genetically resistant mice. J. Immunol. 158, 5338–5348.
Mieza, M. A., Itoh, T., Cui, J. Q., Makino, Y., Kawano, T., Tsuchida, K., et al. (1996) Selective reduction of Vα14+ NK T cells associated with disease development in autoimmune-prone mice. J. Immunol. 156, 4035–4040.
Zeng, D., Dick, M., Cheng, L., Amano, M., Dejbakhsh-Jones, S., Huie, P., et al. (1998) Subsets of transgenic T cells that recognize CD1 induce or prevent murine lupus: role of cytokines. J. Exp. Med. 187, 525–582.
Hammond, K. J. L., Poulton, L. D., Palmisano, L. J., Silveira, P. A., Godfrey, D. I., and Baxter, A. G. (1998) α/β-T cell receptor (TCR)+CD4−CD8−(NKT) thymocytes prevent insulin-dependent diabetes mellitus in nonobese diabetic (NOD)/Lt mice by the influence of interleukin (IL)-4 and/or IL-10. J. Exp. Med. 187, 1047–1056.
Baxter, A. G., Kinder, S. J., Hammond, K. J. L., Scollay, R., and Godfrey, D. I. (1997) Association between αβTCR+CD4−CD8−T cell deficiency and IDDM in NOD/Lt mice. Diabetes 46, 572–582.
Iwakoshi, N. N., Greiner, D. L., Rossini, A. A., and Mordes, J. P. (1999) Diabetes prone BB rats are severly deficient in natural killer T cells. Autoimmunity 31, 1–14.
Tori, M., Ito, T., Yumiba, T., Ohkawa, A., Maeda, A., Sawai, T., et al. (1999) Proliferation of donor-derived NKR-P1A(+) TCR alpha beta (+) (NK T) cells in the nonrecurrent spontaneous diabetic BB rats transplanted with pancreati-coduodenal grafts of Wistar Furth donors. Transplant. Proc. 31, 2741–2742.
Tori, M., Ito, T., Yumiba, T., Maeda, A., Sawai, T., Miyasaka, M., et al. (1999) Significant role of intragraft lymphoid tissues in preventing insulin-dependent diabetes mellitus recurrence in whole pancreaticoduodenal transplantation. Microsurgery 19, 338–343.
Tori, M., Ito, T., Yumiba, T., Ohkawa, A., Maeda, A., Sawai, T., et al. (1999) IL-4 production in IDDM-nonrecurrent pancreas-transplanted BB rats with donor-derived NKR-P1A(+) TCR alpha beta (+) (NK T) cells, but not in IDDM-recurrent BB rats. Transplant. Proc. 31, 1940,1941.
Sumida, T., Sakamoto, A., Murata, H., Makino, Y., Takahashi, H., Yoshida, S., et al. (1995) Selective reduction of T cells bearing invariant Vα24JαQ antigen receptor in patients with systemic sclerosis. J. Exp. Med. 182, 1163–1168.
Maeda, T., Keino, H., Ashara, H., Taniguichi, M., Nishioka, K., and Sumida, T. (1999) Decreased TCR AV24AJ18(+) double-negative T cells in rheumatoid synovium. Rheumatology 38, 186–188.
Vicari, A. P. and Zlotnik, A. (1996) Mouse NK1.1+ T cells: a new family of T cells. Immunol. Today 17, 71–76.
Nicol, A., Nieda, M., Koezuka, Y., Porcelli, S., Suzuki, K., Tadokoro, K., et al. (2000) Dendritic cells are targets for human invariant V alpha 24+ natural killer T cell cytotoxic activity: an important immune regulatory function. Exp. Hematol. 28, 276–282.
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© 2002 Humana Press Inc., Totowa, NJ
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Kent, S.C., Viglietta, V., Hafler, D.A. (2002). Cytokines and Human Type 1 Diabetes. In: Kuchroo, V.K., Sarvetnick, N., Hafler, D.A., Nicholson, L.B. (eds) Cytokines and Autoimmune Diseases. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-129-9_12
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DOI: https://doi.org/10.1007/978-1-59259-129-9_12
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