Table 2 Murine models resembling rheumatoid arthritis.
Proteoglycan-induced arthritis (PGIA) | Streptococcal cell-wall arthritis | Collagen-induced arthritis (CIA) | Antigen- induced arthritis (AIA) | Oil-induced arthritis (OIA) | TNF-α tg | IL-1ra KO | K/BxN tg | ||
|---|---|---|---|---|---|---|---|---|---|
MODEL | Murine disease | Immune-mediated joint disease | Biphasic, immune-mediated joint-disease Acute phase: T-cell independent Chronic phase: T-cell dependent | Chronic T-cell driven immune-mediated joint disease | Acute, locally limited, self-limiting antigen-specific T-cell driven joint disease | T-cell driven, self-limiting polyarthritis | Chronic, erosive, T- and B-cell independent polyarthritis | Chronic, T-cell driven inflammatory polyarthro-pathy | Severe Th2-driven inflammatory arthritis |
MODIFICATIONS | (Transgenic) modifications | None | None | None | None | None | Increased TNFα-transcript stabilization | Deletion exons of IL-1ra | Transgenic TCR and MHC class II allele Ag7 |
Mutation type/treatment | i.p. cartilage proteoglycan | i.p. peptidoglycan-polysaccharide polymers | i.d. type II collagen in complete Freund’s adjuvant | e.g. s.c./i.a. methylated bovine serum albumin | i.d. injection of incomplete Freund’s adjuvant | Germline | Germline | Germline | |
Spont./ transp./ind. | Ind. | Ind. | Ind. | Ind. | Ind. | Spont. | Spont. | Spont. | |
PHENOTYPE | Strain | BALB/c | Lewis rats | e.g. DBA/1 | e.g. C57BL/6 BALB/c | DA rats | C57BL/6 | BALB/c | C57BL/6xNOD |
Weight loss | NA | NA | NA | NA | NA | Y | NA | NA | |
Spleno-megaly | NA | NA | Y | NA | NA | NA | Y | Y | |
Lymph-adenopathy | NA | NA | Y | NA | NA | NA | Y | NA | |
WBC count | NA | NA | NA | NA | NA | NA | NA | NA | |
Median overall survival | NA | NA | NA | Recovery 21 d post-injection | Recovery 45 d post-injection | 84-98 wk (tg197) | NA | NA | |
LEUKEMIA | Leukemic expansion | N | N | N | N | N | N | N | N |
Clonality relevant T-cell population | NA | NA | NA | NA | Y | NA | NA | NA | |
IMMUNITY | Immuno-competent | Y | Y | Y | Y | Y | Y | Y | Immunocompromised |
Auto-antibodies | Y | NA | Y | Y | N | NA | Y | Y | |
Infiltration of lymphocytes in peripheral organs (other than joints) | NA | NA | NA | NA | N | Y | N | N | |
Inflammation | Joint | Joint | Joint | Joint | Joint | Joint Liver Kidney Small intestine | Joint | Joint | |
CYTOKINES | Cytokines, increased (↑) or otherwise relevant in pathogenesis | IFN-γ IL-6 IL-1β | NA | IL-1β TNF-α ↑ IFN-γ ↑ IL-6 | IL-6 | IL-2 IFNγ TNFα | hTNFα | IL-17 IL-6 TNFα COX2 | IL-1 TNFα |
IMMUNOPHENOTYPE | All T | NA | ↓ | ↑ (joint) | NA | NA | NA | Not altered | ↓ |
Immature T | NA | NA | NA | NA | NA | NA | NA | NA | |
CD8+ T | NA | NA | ↑ (joint) | NA | NA | NA | Not altered | NA | |
CD8+ memory T | NA | NA | NA | NA | NA | NA | NA | NA | |
CD4+ T | NA | NA | ↑ (joint) | NA | Essential for pathogenesis | NA | Not altered | ↑ (joint) | |
Other immune cell populations | NA | B cells ↓ Activated B-cell compartment % Monocytes↑ | B cells (PB, LN) ↑ Activated B-cell compartment % Myeloid cells ↑ (PB, LN) | NA | Neutrophils ↑ | B-cell independent disease | No alteration in T:B ratio ↑ IgG ↑ IgE Neutrophils↑ (joints) | B cells ↑ Hypergammaglobulinemia | |
Original reference | [68] | [69] | [70] | [71] | [72] | [73] | [59] | [56] |
