Table 1.
Autoimmune studies with HIS hu-mice.
| Strain | Additional genetic manipulation | Model and human cell/tissue source | Autoimmune studies |
|---|---|---|---|
| CB17Scid | None | Hu-(skin T cells) – skin T cells reactive with hair follicles + hairless scalp biopsies from alopecia patients | Alopecia areata: hairless scalp biopsies regrew hair in few weeks after engrafting into SCID mice. Intra-dermal injection of in vitro activated skin T cells from patients reduced hair growth (132) |
| NODScid | None | Hu-(blood T cells&APCs) – islet-reactive T cell clones + HLA-matched peptide-pulsed APCs from healthy PBMCs | T1D: streptozotocin treatment before T cell adoptive transfer; islet-reactive T cell clones homed to pancreas tissue in the presence of peptide-loaded APCs (121) |
| None | Hu-(synovium) – inflamed synovium from RA patients | RA: Blocking BLyS and APRIL modulated B and T cell function in the engrafted synovium. Stimulatory effects were observed when synovium contained germinal center structures. (127) | |
| NODScid Il2rγ−/- (NSG) | None | Hu-PBL – PBMCs from SjS patients | SjS: local inflammation in salivary and lacrimal glands with increased production of inflammatory cytokines in mice transferred with patients PBMCs (130) |
| None | Hu-PBL – healthy PBMCs | EAE/MS: adoptive transfer of PBMCs and myelin primed human DCs followed by immunization with myelin peptides in CFA; observed subclinical CNS inflammation (131) | |
| HLA-DR4 transgene | Hu-(blood T cells) – CD4 T cells from either T1D or control patients with T1D associated HLA-DR4 | T1D: CD4 T cell stimulated with pancreas peptides; healthy and T1D T cells homed to pancreas; reduced insulin production in pancreas of hu-mice that received T1D T cells (123) | |
| None | Hu-HSCs (FL) | SLE: pristane injection; observed lupus-like disease with ANA production and lupus nephritis (118) | |
| MHC II KO; HLA-DR1 transgene | Hu-HSCs (BM) – HSCs from IPEX patient | IPEX: spontaneous multi-organ systemic and fatal autoimmunity (119) | |
| None | Hu-HSCs (CB) | RA: CFA injection into joints; observed clinical and histological RA with inflammatory infiltrate, swelling and bone erosion (129) | |
| None | Hu-HSCs (FL) | Anti-CTLA4 immunotherapy: observed autoimmune hepatitis, liver lymphocytic infiltration, ANA production, T cell activation, weight loss (144) | |
| None | Hu-HSCs (FL) | Anti-CTLA4 or PD1 immunotherapy: observed massive lymphocytic infiltration in many tissues and weight loss but only in mice treated with anti-CTLA4 (143) | |
| MHC II KO; HLA-DQ8 transgene | Hu-HSCs (CB) – HLA-DQ8+ HSCs | T1D vaccine study: infusion of insulin mimetopes induces functional Foxp3+ Tregs that suppress insulin-reactive effector T cells (125) | |
| None | Hu-BLT – BM HSCs from T1D patients and T1D-relevant HLA-matched FT | T1D: observed increased proportion of activated and memory T cells with T1D-derived bone marrow HSCs (62) | |
| MHC II KO; HLA-DQ8 transgene | Hu-BLT –HLA-DQ8+ FL HSCs and FT | T1D: streptozotocin treatment before transfer of insulin-reactive CD4 T cells and insulin peptide immunization in CFA; observed insulitis and diabetes (124) | |
| None or pig cytokine transgenes (IL-3, GM-CSF, SCF) | Hu-BLT – BM HSCs from T1D or RA patients and disease-relevant HLA-matched FT | T1D and RA: observed increased frequency of autoreactive and polyreactive B cells (122) | |
| NOD/Shi-scid/IL-2Rγnull (NOG) | None | Hu-HSCs (CB) | RA: low dose of EBV infection; observed erosive arthritis closely related to RA with pannus formation and inflammatory infiltrate in the synovium (128) |
| None or with human cytokine transgenes (IL-3, GM-CSF) | Hu-BLT – FL HSCs and FT | Anti-PD1 immunotherapy: observed pneumonitis, hepatitis, nephritis, dermatitis, adrenalitis, T cell activation (145) |
BM = bone marrow; CB = cord blood; FL = fetal liver; FT = fetal thymus; HSCs = hematopoietic stem cells; ANA = anti-nuclear antibodies.