In healthy primates, circulating autoreactive T cells mediate autoimmune disease.

Genain, Claude P.; Lee-Parritz, David; Nguyen, My-Hoa; Massacesi, Luca; Joshi, Neha; Ferrante, Robert J.; Hoffman, Kathleen; Moseley, M. Allen; Letvin, Norman L.; Hauser, Stephen L.

doi:10.1172/jci117454

Cited by 89 publications

(69 citation statements)

References 38 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results of T cell and Ab epitope mapping are in line with data from Genain et al (5,6,28). On the basis of the data discussed thus far, we conclude that phMOG14 -36 may contain critical T and B cell epitopes for the initiation of EAE in common marmosets.…”

Section: Discussionsupporting

confidence: 91%

“…The pathogenesis of EAE in common marmosets involves, as in rodents, at least two separate pathogenic pathways. CNS inflammation can be mediated by T cell reactivity to major myelin Ags such as MBP or proteolipid protein (6,7). CNS demyelination, however, requires the involvement of Abs, in particular those directed to MOG (7, 9, 18 -20).…”

Section: Discussionmentioning

confidence: 99%

“…The clinical and pathological expression of myelin-induced EAE in marmosets is thought to result from a synergy of cellular and humoral autoimmune reactivity predominantly directed against two Ags, namely myelin basic protein (MBP) (2,6,7) and myelin/oligodendrocyte glycoprotein (MOG) (7)(8)(9). Hence, for the purpose of the present study, three marmoset twin couples were randomly selected from our colony; one sibling of each twin was immunized with recombinant human MOG (rhMOG), and the other sibling was immunized with purified human MBP (hMBP).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Myelin/Oligodendrocyte Glycoprotein-Induced Autoimmune Encephalomyelitis in Common Marmosets: The Encephalitogenic T Cell Epitope pMOG24–36 Is Presented by a Monomorphic MHC Class II Molecule

Brok

Uccelli

Rosbo

et al. 2000

The Journal of Immunology

115

130

View full text Add to dashboard Cite

Immunization of common marmosets (Callithrix jacchus) with a single dose of human myelin in CFA, without administration of Bordetella pertussis, induces a form of autoimmune encephalomyelitis (EAE) resembling in its clinical and pathological expression multiple sclerosis in humans. The EAE incidence in our outbred marmoset colony is 100%. This study was undertaken to assess the genetic and immunological basis of the high EAE susceptibility. To this end, we determined the separate contributions of immune reactions to myelin/oligodendrocyte glycoprotein (MOG) and myelin basic protein to the EAE induction. Essentially all pathological features of myelin-induced EAE were also found in animals immunized with MOG in CFA, whereas in animals immunized with myelin basic protein in CFA clinical and pathological signs of EAE were lacking. The epitope recognition by anti-MOG Abs and T cells were assessed. Evidence is provided that the initiation of EAE is based on T and B cell activation by the encephalitogenic phMOG14–36 peptide in the context of monomorphic Caja-DRB*W1201 molecules.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Myelin/Oligodendrocyte Glycoprotein-Induced Autoimmune Encephalomyelitis in Common Marmosets: The Encephalitogenic T Cell Epitope pMOG24–36 Is Presented by a Monomorphic MHC Class II Molecule

Brok

Uccelli

Rosbo

et al. 2000

The Journal of Immunology

115

130

View full text Add to dashboard Cite

show abstract

“…Self-reactive lymphocytes are a normal component of the immune systems of healthy organisms (54,55), and the intriguing possibility of regulating these lymphocytes would impact the control of autoimmunity and promote cancer immunotherapy. Most research characterizing self-reactive lymphocytes has focused on how the various mechanisms of tolerance induction affect the fate of T lymphocytes that demonstrate high affinity for self.…”

Section: Discussionmentioning

confidence: 99%

Characterization of CD8+ T Lymphocytes That Persist After Peripheral Tolerance to a Self Antigen Expressed in the Pancreas

Nugent

Morgan

Biggs

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

As a result of expression of the influenza hemagglutinin (HA) in the pancreatic islets, the repertoire of HA-specific CD8+ T lymphocytes in InsHA transgenic mice (D2 mice expressing the HA transgene under control of the rat insulin promoter) is comprised of cells that are less responsive to cognate Ag than are HA-specific CD8+ T lymphocytes from conventional mice. Previous studies of tolerance induction involving TCR transgenic T lymphocytes suggested that a variety of different mechanisms can reduce avidity for Ag, including altered cell surface expression of molecules involved in Ag recognition and a deficiency in signaling through the TCR complex. To determine which, if any, of these mechanisms pertain to CD8+ T lymphocytes within a conventional repertoire, HA-specific CD8+ T lymphocytes from B10.D2 mice and B10.D2 InsHA transgenic mice were compared with respect to expression of cell surface molecules, TCR gene utilization, binding of tetrameric KdHA complexes, lytic mechanisms, and diabetogenic potential. No evidence was found for reduced expression of TCR or CD8 by InsHA-derived CTL, nor was there evidence for a defect in triggering lytic activity. However, avidity differences between CD8+ clones correlated with their ability to bind KdHA tetramers. These results argue that most of the KdHA-specific T lymphocytes in InsHA mice are not intrinsically different from KdHA-specific T lymphocytes isolated from conventional animals. They simply express TCRs that are less avid in their binding to KdHA.

show abstract

“…jacchus closely resembles MS with respect to clinical presentation, white matter lesion formation in vivo as Ž . assessed by magnetic resonance imaging MRI , and CNS Ž histopathology Genain et al, 1994;McFarland, 1994;Genain et al, 1995;Massacesi et al, 1995;Genain et al, . 1996 .…”

Section: žmentioning

confidence: 99%

Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

Laman

Meurs²,

Schellekens³

et al. 1998

Journal of Neuroimmunology

View full text Add to dashboard Cite

Ž .Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis MS and experimental autoimmune Ž . encephalomyelitis EAE in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefore, we analysed the expression of selected accessory molecules and cytokines in the brain of Ž . marmoset monkeys Callithrix jacchus with acute EAE, a newly described non-human primate model for MS. All animals experienced active disease clinically and histopathologically with strong resemblance to MS. Perivascular infiltrates of mononuclear cells showed abundant expression of CD40. CD40 was expressed on macrophages, indicating that T cell priming and macrophage effector functions Ž . Ž . may result from local CD40-CD40L interactions. CD40 ligand CD40L and B7-2 CD86 were also expressed, but to a lower extent, Ž . while B7-1 CD80 expression was limited. Both pro-inflammatory and anti-inflammatory cytokines were produced within individual Ž . lesions during active disease IFN-a, IFN-g , TNF-a, IL-1a , IL-1b, IL-2, IL-4, IL-10 and IL-12 . This suggests that relative levels rather than sequential expression of Th1-and Th2-type cytokines determine disease activity. These findings demonstrate the value of EAE in marmoset monkeys as a model to assess the role of accessory molecules and cytokines in multiple sclerosis, and to evaluate targeted intervention. q

show abstract

In healthy primates, circulating autoreactive T cells mediate autoimmune disease.

Cited by 89 publications

References 38 publications

Myelin/Oligodendrocyte Glycoprotein-Induced Autoimmune Encephalomyelitis in Common Marmosets: The Encephalitogenic T Cell Epitope pMOG24–36 Is Presented by a Monomorphic MHC Class II Molecule

Myelin/Oligodendrocyte Glycoprotein-Induced Autoimmune Encephalomyelitis in Common Marmosets: The Encephalitogenic T Cell Epitope pMOG24–36 Is Presented by a Monomorphic MHC Class II Molecule

Characterization of CD8+ T Lymphocytes That Persist After Peripheral Tolerance to a Self Antigen Expressed in the Pancreas

Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

Contact Info

Product

Resources

About