Immunotherapy of type 1 diabetes: lessons for other autoimmune diseases

Bach, Jean-François

doi:10.1186/ar554

Arthritis Research & Therapy

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]
Antilymphocyte globulin [11, 45]	7 Pharmacologically active cytokines
Neonatal thymectomy [46]	7.1 IL-4 [86]
1.2 Sequestration/diversion	7.2 IL-10 [87, 88]
Anti-CD43 [47]	7.3 IL-13 [89]
Anti-VLA-l [48]	7.4 IL-3 [37]
Anti-VLA-4 [48, 49]	7.5 G-CSF (F Zavala, unpublished observations)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]	Intranasal [34, 95]
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]	Inactive analogue [95, 97]
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-A [16, 66]	P277 peptide [108, 109]
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]
Anti-IFN-γ [74, 75]	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]	α-Galactosylceramide [33, 124]
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]
DNA vaccination [98, 105]	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)	Cholera toxin B [156, 157]
10.5 IFN-γR/IgGl fusion protein [76, 130]	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]	Natural antibodies [161, 162]
Allogeneic [136] (+ immunosuppression)	Lupus idiotype [163]
11.2 Intrathymic islet transplantation [38]	Lipopolysaccharide [164, 165]
11.3 Bone marrow transplantation	13.4 Diet
Allogeneic [137, 138]	Casein hydrolysate [166, 167]
Syngeneic [37]	13.5 Other
11.4 Dendritic cells [139, 140]	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-Ia^g7[143]	Ganglioside [171]
11.7 Allogeneic cells	Antiasialo GM-1 antibody [172]
Macrophages [144]	Hyaluronidase [42]
Spleen cells [36]	Concanavalin A [173]

CD45RA(B), CD45 receptor A(B); CDXXL, CDXX ligand; CFA, complete Freund's adjuvant; GAD, glutamic acid decarboxylase; G-CSF, granulocyte-colony-stimulating factor; ICAM-1, intercellular adhesion molecule-1; IFN, interferon; MHC, major histocompatibility complex; TCR, T-cell receptor; V, variable region (of immunoglobulin); VLA, very late antigen.

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