TABLE 2 Studies that have investigated the role of regulatory T cells in mouse models of CNS autoimmunity.
From the following article:
The role of regulatory T cells in multiple sclerosis
Alla L Zozulya and Heinz Wiendl
BACK TO ARTICLE| Experimental approach | Mouse model | Key findings | Comments | References |
|---|---|---|---|---|
Abbreviations: EAE, experimental autoimmune encephalomyelitis; Ig, immunoglobulin; MBP, myelin basic protein; MOG, myelin oligodendrocyte glycoprotein; PLP, proteolipid protein; RAG, recombination activating gene; Tg, transgenic; TCR, T-cell receptor; TR1, T-regulatory 1; TREG, regulatory T. | ||||
| Discovery of TREG cell function during CNS autoimmunity | ||||
| Transfer of high numbers of purified TREG cells from naive wild-type mice | MOG-induced EAE in C57Bl/6 mice PLP-induced EAE in SJL mice | Prevention of active and adoptive EAE Prevention of active EAE | First evidence of a role for naturally occurring TREG cells in preventing the onset and/or progression of active and adoptive EAE induced by autoreactive T-helper 1 cell immunization First evidence of a role for IL-10 in regulatory function | Kohm et al. (2002)20 Zhang et al. (2004)23 |
| Transfer of CNS-derived TREG cells from mice recovering from EAE | MOG-induced EAE in C57Bl/6 mice | Prevention of active EAE | First 'direct' demonstration of TREG-cell role in the natural resolution of CNS autoimmunity at the effector site | McGeachy et al. (2005)21 |
| Transfer of peripheral TREG cells from EAE animals | Chronic MOG-induced EAE in LEW.1AV1 rats | Suppression of chronic EAE development | Follow-up study; first demonstration of importance of TREG cells during the chronic phase of EAE | Matsumoto et al. (2007)32 |
| CD4+CD25+ peripheral TREG cells from non-Tg or TCR Tg MBP/Rag1+/+ mice | TCR Tg MBP/Rag1-/- mice | Prevention of spontaneous EAE | First demonstration of a preventive effect of adoptively transferred antigen-specific TREG cells | Hori et al. (2003)19 |
| TREG-cell depletion by anti-CD25 antibody treatment | MOG-induced EAE in C57Bl/6 mice PLP-induced EAE in SJL mice | Increased susceptibility to reinduction of EAE No secondary remissions during EAE course | First experiments with TREG-cell ablation | McGeachy et al. (2005)21 Zhang et al. (2004)23 Gartner et al. (2006)33 |
| Transfer of Ig–PLP1-expanded 5B6 TCR Tg PLP-specific T cells | Passive PLP-induced EAE in Rag2-/- and wild-type SJL mice EAE induced by MOG and MBP | Complete reversion of PLP-induced EAE No effect of PLP-specific TREG cells | Evidence that activation of TREG cells by the cognate autoantigen is necessary for operation of broad suppressive functions | Yu et al. (2005)22 |
| Therapeutic manipulations to expand and modulate TREG-cell populations during EAE | ||||
| Vitamin D3 and dexamethasone-treated ovalbumin-specific TR1 cells | Mouse spinal cord homogenate-induced EAE in BALB/c mice | Prevention of active EAE | One of the first attempts to beneficially manipulate TREG-cell function | Barrat et al. (2002)37 |
| Animals treated with a CD28 superagonist that preferentially promotes TREG-cell expansion | MOG-induced EAE in C57Bl/6 mice | Prevention of acute and chronic EAE | CD28 superagonist acts via expansion of TREG cells; active at very low doses; potential for therapeutic use | Beyersdorf et al. (2005)42 |
| TR1 cells induced by B7-H1 immunoglobulin fusion protein and immobilized CD3-specific antibody | MOG-induced EAE in C57Bl/6 mice | Prevention of active EAE | Coinhibitory molecule B7-H1 induces differentiation of beneficial TR1 cells | Ding et al. (2006)38 |
| T-helper 3 cells induced by bacterial vaccine (myelin-independent antigen) | PLP-induced EAE in SJL mice | Reduction of EAE development | Disease-irrelevant TREG cells seem to be effective in prevention of CNS autoimmunity | Ochoa-Reparaz et al. (2007)41 |
| Intravenous-immunoglobulin-related expansion of natural TREG cells | MOG-induced EAE in C57Bl/6 mice | Prevention of active EAE | Provides a rationale to test intravenous immunoglobulin as an immunomodulatory tool to enhance TREG-cell function during early onset of multiple sclerosis | Ephrem et al. (2008)39 |
Induction of forkhead box protein P3 in TREG cells by 17 -estradiol | MOG-induced EAE in C57Bl/6 mice | Reduction of EAE clinical signs | First work showing protective effect of 17-estradiol in EAE | Matejuk et al. (2004)40 |
| TREG cells induced by type II monocytes under glatiramer acetate treatment | MOG-induced EAE in C57Bl/6 mice | Amelioration of EAE clinical signs | Shows indirect involvement of TREG cells in beneficial action of glatiramer acetate on EAE through antigen-nonspecific mechanism | Weber et al. (2007)78 |