Table 1 Immunotherapeutic agents or other treatments used in NOD mice
From: Immunotherapy of type 1 diabetes: lessons for other autoimmune diseases
1 T-cell depletion or sequestration/diversion | 6.3 IL-12 |
1.1 Depletion | Anti-IL-12 [80] |
Anti-CD3 [28] | IL-12 antagonist (p40)2 [81] |
Anti-CD4 [40] | 6.4 IFN-α (oral) [82] |
Anti-CD8 [41] | 6.5 IL-1 |
Anti-CD44 [42] | IL-1 antibody [83] |
Anti-CD45RA [43] | IL-1 antagonist [84] |
Anti-CD45RB [44] | 6.6 IL-6 [75] |
Anti-Thy l.2 [45] | 6.7 Lymphotoxin receptor [85] |
7 Pharmacologically active cytokines | |
Neonatal thymectomy [46] | 7.1 IL-4 [86] |
1.2 Sequestration/diversion | |
Anti-CD43 [47] | 7.3 IL-13 [89] |
Anti-VLA-l [48] | 7.4 IL-3 [37] |
7.5 G-CSF (F Zavala, unpublished observations) | |
VLA-4/Ig fusion protein [50] | 7.6 Lymphotoxin [90] |
Anti-CD62L [49] | 7.7 IL-11 [91] |
2 Blockade of T-cell activation | 7.8 IL-1α [92] |
2.1 Chemical immunosuppressants | 7.9 TNF-α [26] |
Cyclosporin A [51] | 8 Tolerance to soluble β-cell autoantigens |
FK-506 [52] | 8.1 Insulin |
Azathioprine [53] | Oral [93] |
Rapamycin [54] | Oral + IL-10 [94] |
Deoxyspergualin [55] | |
2.2 γ Irradiation [56] | Subcutaneous |
3 Targeting of T-cell receptors | Native protein [96] |
3.1 TCRαβ antibody [13] | B chain [96] |
3.2 CD3 antibody [28] | |
3.3 Vβ8 antibody [57] | DNA vaccination [98] |
3.4 T-cell vaccination | Gene-transfer delivery [99] (proinsulin gene) |
Polyclonal activated T cells [58] | Cholera-toxin conjugate [100] |
Glutaraldehyde-treated T cells [59] | 8.2 Glutamic acid decarboxylase (GAD) |
Activated T cells | Oral [101] |
Vβ8 T cells [60] | Intranasal [102] |
Anti-hsp60 T-cell clone [61] | Subcutaneous [103] |
3.5 Blocking peptides [62] | Intrathymic [104] |
4 Targeting of MHC molecules | DNA vaccination [105] |
4.1 Anti-class-I [63] | Anti-GAD antibody [106] |
4.2 Anti-class-II [64] | 8.3 Heat shock protein 60 (hsp60) |
4.3 MHC transgenic mice | Subcutaneous or intraperitoneal |
Class I [65] | Protein [107] |
I-E [67] | Gene-transfer delivery [110] |
5 Targeting of costimulation and adhesion molecules | 8.4 Pancreatic extracts (oral) [111] |
5.1 Costimulation molecules | 9 Stimulation of regulatory T cells |
Anti-CD28 [68] | 9.1 Pathogens |
CTLA-4–Ig fusion protein [69] | Bacteria |
Anti-B7.2 [69] | Mycobacteria |
Anti-CD40L [70] | Mycobacterium bovis[112] |
5.2 Adhesion molecules | M. avium[113] |
Anti-ICAM-1 [71] | Complete Freund's adjuvant [114] |
Soluble ICAM-1 | Lactobacillus casei[115] |
Recombinant protein [72] | Streptococcal extract [116] |
Gene therapy (P Lemarchand, unpublished observations) | Klebsiella extract [117] |
Anti-Mac [73] | Escherichia coli (+ oral insulin) [118] |
Anti-LFA-l [71] | Viruses |
6 Cytokine blockade | Mouse hepatitis virus [119] |
6.1 IFN-γ | Lactate dehydrogenase virus [120] |
Lymphocytic choriomeningitis virus [121] | |
IFN-γR/IgG1 fusion protein [76] | Parasites |
6.2 IL-2 | Filariae [122] |
Anti-IL-2R [77] | Schistosomes [123] |
IL-2R/Ig fusion protein [78] | 9.2 Stimulation of innate immunity |
IL-2 diphtheria-toxin protein [79] | |
9.3 Nondepleting anti-T-cell antibodies | 12 Inhibition of β-cell lesion |
Anti-CD3 [28] | 12.1 Nicotinamide [145] |
Anti-CD4 [30] | 12.2 Antioxidants |
Superantigens [125] | Vitamin E [146] |
10 Gene therapy | Probucol analog [147] |
10.1 β-cell antigens | Probucol + deflazacort [148] |
Aminoguanidine [149] | |
GAD immunoglobulin [126] | 12.3 Anti-inflammatory agents |
10.2 IL-4 | Pentoxifylline [150] |
Retrovirus (T-cell transfection) [127] | Rolipram [150] |
Biolistic [128] | 13 Miscellaneous |
Adenovirus [129] | 13.1 Immunomodulators |
IL-4/IgG1 fusion protein [130] | Linomide [151] |
10.3 IL-10 | Ling-zhi-8 [152] |
T-cell transfection [131] | D-Glucan [153] |
Local [132] | Multi-functional protein 14 [154] |
Systemic [133] | Ciamexon [155] |
10.4 ICAM-1 (P Lemarchand, in preparation) | |
Vanadate [158] | |
10.6 TGF-β [134] | Vitamin D3 analogue [159] |
10.7 Calcitonin [135] | 13.2 Hormones and related proteins |
11 Cell therapy | Androgens [160] |
11.1 Islet or segmental pancreas transplantation (+ immunosuppression) | IGF-I [153] |
13.3 Immunomanipulation | |
Syngeneic [12] | |
Allogeneic [136] (+ immunosuppression) | Lupus idiotype [163] |
11.2 Intrathymic islet transplantation [38] | |
11.3 Bone marrow transplantation | 13.4 Diet |
Syngeneic [37] | 13.5 Other |
Sulfatide [168] | |
11.5 Natural killer T cells [141] | Bee venom [90] |
11.6 CD4 cell lines | Kampo formulation [169] |
Polyclonal [142] | Silica [170] |
Anti-Iag7[143] | Ganglioside [171] |
11.7 Allogeneic cells | Antiasialo GM-1 antibody [172] |
Macrophages [144] | Hyaluronidase [42] |
Spleen cells [36] | Concanavalin A [173] |