• between 15% and 20% of mice develop spontaneous EAE

• disease started between 7 and 10 weeks of age, with classical paralytic EAE signs

• in a minority of cases, with a spastic component

• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues

• inflammatory infiltrates in the peripheral nervous system despite the absence of MOG within these tissues

• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve

• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in the spinal cord

• within the spinal cord and optic nerve

• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve

• 15% of the mice develop spontaneous EAE

• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues

• disease started between 7 and 10 weeks of age, with classical paralytic EAE signs

• fifty percent spontaneously develop opticospinal myelitis

• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues

• in a minority of cases, with a spastic component

• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues

• inflammatory infiltrates in the peripheral nervous system despite the absence of MOG within these tissues

• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve

• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in the spinal cord

• within the spinal cord and optic nerve

• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve

• in conjunction with anti-CTLA-4 antibody treatment, mice exhibit reduced paralysis induced by experimental autoimmune encephalomyelitis (EAE) compared to wild type mice

• however, adoptive transfer of Gt(ROSA)26Sor^tm2Awai Cd19^tm1(cre)Cgn double heterozygous B cells increases paralysis induced by EAE despite treatment with anti-CTLA-4 antibodies compared to wild-type mice receiving Gt(ROSA)26Sor^tm2Awai Cd19^tm1(cre)Cgn double heterozygous B cells

• disease started between 7 and 10 weeks of age, with classical paralytic EAE signs

• between 15% and 20% of mice develop spontaneous EAE

• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues

• in a minority of cases, with a spastic component

• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues

• inflammatory infiltrates in the peripheral nervous system despite the absence of MOG within these tissues

• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve

• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in the spinal cord

• within the spinal cord and optic nerve

• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve

• spontaneous EAE develops in two out of six mice

• CD4 T cells are highly susceptible to dose-dependent suppression by CD8 T regulatory cells in vitro

• this suppression is dependent on Fas ligand being expressed by the CD8 T regulatory cell

• transfer of CD4 T cells into Rag2^-/^- Prf1^-/^- hosts initiates a progressive and lethal form of EAE that results in death from fulminant disease within 14?16 days after transfer

• co-transfer of CD8 T regulatory cells with mutant CD4 T cells prevents disease where as co-transfer of CD8 T regulatory cells with transgenic CD4 T cells not carrying the H2-T23 mutation fails to prevent disease

• CD4 T cells are fully resistant to suppression by CD8 T regulatory cells in vitro as measured by proliferation and IL-2 secretion

• unlike Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• in CD4+ T cells stimulated with anti-CD3

• under nonpolarizing conditions

• in CD4+ T cells under nonpolarizing conditions

• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control but not as much as in cells from Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control but not as much as in cells from Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• IL2 levels from CD4+ T cells stimulated with MOG35-55 do not persist as long as in cells from wild-type mice

• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control but not as much as in cells from Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• in CD4+ T cells stimulated with anti-CD3

• in CD4+ T cells stimulated with anti-CD3

• under nonpolarizing conditions

• under Th17 polarizing conditions

• of CD4+ T cells stimulated with anti-CD3

• in CD4+ T cells stimulated with MOG35-55, rested then restimulated with MOG35-55 compared with cells from wild-type control and Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• under nonpolarizing conditions, Th1 cells are reduced 50% compared to in wild-type but are 3-fold higher than in Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• in T cells cultures stimulated with MOG35-55

• 50% under Th17 polarizing conditions compared with wild-type control and Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• in T cells cultures stimulated with MOG35-55

• under Th2 polarizing conditions compared with wild-type controls and Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• in CD4+ T cells under nonpolarizing conditions

• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control and Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• IL10 levels in T cells stimulated with MOG35-55 rise and contract unlike in cells from wild-type control and Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice where levels continue to rise

• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control and Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• IL2 levels from T cells stimulated with MOG35-55 do not increase beyond day 1unlike in cells from wild-type control

• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control and Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• under Th17 polarizing conditions

• of CD4+ T cells stimulated with anti-CD3

• in CD4+ T cells stimulated with MOG35-55, rested then restimulated with MOG35-55 compared with cells from wild-type control and Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• of CD4+ T cells stimulated with anti-CD3

• in CD4+ T cells stimulated with MOG35-55, rested then restimulated with MOG35-55 compared with cells from wild-type control and Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• under nonpolarizing conditions, Th1 cells are reduced 50% compared to in wild-type but are 3-fold higher than in Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• in T cells cultures stimulated with MOG35-55

• 50% under Th17 polarizing conditions compared with wild-type control and Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• in T cells cultures stimulated with MOG35-55

• under Th2 polarizing conditions compared with wild-type controls and Cd5^tm1Cgn/Cd5^tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

• 40% of transgenic mice succumb to EAE compared to no non-transgenic littermates

• 7/15 mice without EAE show typical myelinating/demyelinating lesions of optic neuritis

• mice with EAE show typical myelinating/demyelinating lesions of optic neuritis

• 55 and 78% of transgenic mice immunized with 100 and 10 ug of MOG 35-55 without PT, respectively, develop optic nerve lesions

• mice with or without EAE that display optic neuritis have myelinating/demyelinating lesions consisting of subpial and endoneurial mononuclear cell infiltrates with demyelination indicated by presence of foamy macrophages

• CNS tissues show myelin loss

• mice with optic neuritis have varying degrees of axonal injury and loss

• superficial eye lesions in mice without EAE are often associated with progressive atrophy of the eye

• 67% of mutants show these eye lesions compared to no wild-type

• mice without EAE show eyelid inflammation and eyelid swelling; this is unilateral and not observed in wild-type littermates during up to 1 year observation

• mice without EAE develop superficial inflammation around the eyelids; this is unilateral and not observed in wild-type littermates during up to 1 year observation

• mice with or without EAE that display optic neuritis have myelinating/demyelinating lesions consisting of subpial and endoneurial mononuclear cell infiltrates with demyelination indicated by presence of foamy macrophages

• CD4/CD8 single positive ratio in thymus of transgenic mice is biased toward CD4+ compartment

• analysis shows a skewing toward CD4+ T cells in spleens as well

• spleen cells from naive mice produce high levels of IFN gamma in response to MOG 35-55

• 4% (3/72) of mice develop spontaneous EAE, indicated initially by a limp tail, followed by hindlimb paralysis between 2.5 and 5 months of age

• 55 and 78% of mice immunized with 100 and 10 ug of MOG 35-55 without PT, respectively, develop optic nerve lesions

• mice with disease have typical myelinating/demyelinating lesions

• transgenic mice immunized with MOG 35-55 + pertussis toxin (PT) develop more severe EAE than non-transgenic littermates, with earlier onset and greater clinical scores; 50% of mice develop associated optic neuritis also

• injection of PT alone induces clinical EAE in 39% and histological EAE in 56% of transgenics compared to no non-transgenic mice; 80% of mice develop associated optic neuritis also

• 7/15 mice without EAE show typical myelinating/demyelinating lesions of optic neuritis

• mice with EAE show typical myelinating/demyelinating lesions of optic neuritis

• 55 and 78% of transgenic mice immunized with 100 and 10 ug of MOG 35-55 without PT, respectively, develop optic nerve lesions

• mice without EAE develop superficial inflammation around the eyelids; this is unilateral and not observed in wild-type littermates during up to 1 year observation

• CD4/CD8 single positive ratio in thymus of transgenic mice is biased toward CD4+ compartment

• analysis shows a skewing toward CD4+ T cells in spleens as well

• spleen cells from naive mice show increased proliferative response to myelin oligodendrocyte protein peptide 35-55 (MOG 35-55) compared to wild-type mice

• EAE-affected mice showed edema in the brain and spinal cord

• mice without EAE show eyelid inflammation and eyelid swelling; this is unilateral and not observed in wild-type littermates during up to 1 year observation

• T cells incubated with LPS-stimulated CD11c+ dendritic cells with IL-23 in the presence of MOG peptide and neutralizing antibodies against IFN-gamma and IL-4 plus either IL-25 or IL-13 antibodies produce less IL-17 than with both IL-25 and IL-13 antibodies or without either