Regulation of CNS inflammation upon T cell interaction with CNS resident cells

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Abstract

Multiple Sclerosis (MS), is a neurologic, autoimmune disease characterized by CNS immune cell infiltration and demyelination. To experimentally study MS, we have utilized the mouse model Experimental Autoimmune Encephalomyelitis (EAE). EAE is induced through immunization with myelin antigens, which elicits an autoreactive Th1 cell response. Encephalitogenic T cells migrate into the CNS where they receive antigen specific restimulation via CNS specific APCs, which causes inflammation and demyelination. Our aim with the present study was to investigate various aspects of T cell regulation in EAE. The potential immunoregulatory role of CD1d restricted T cells was evaluated using CD1d deficient mice (CD1-/-). Our results suggests that CD1d restricted T cells regulate EAE, both through down-regulation of peripheral autoreactive T cell cytokine responses and through up-regulation of TGF-beta1 production within the CNS. Next, we investigated the regulatory pathway mediated by IFN-beta, a common treatment for MS. From the results we concluded that IFN-beta is expressed in the CNS upon inflammation, where it represses glial cell activation and capacity to re-stimulate infiltrating encephalitogenic T cells. Furthermore, we could show that IFN-beta increases the glial cell expression of CD1d. IFN-beta has also been implicated to be important in the induction of oral tolerance, however, by using IFN-beta-/- mice and EAE, we showed that oral tolerance induction is not dependent on IFN-beta. Finally, in a study designed to evaluate possible immunoregualatory functions of neurons, we demonstrated that upon interaction with TGF-beta1 producing neurons, encephalitogenic T cells aquire a regulatory phenotype with the capacity to inhibit EAE development.

Detaljer

Författare
  • Ingrid Teige
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området

Nyckelord

Originalspråkengelska
KvalifikationDoktor
Tilldelande institution
Handledare/Biträdande handledare
  • [unknown], [unknown], handledare, Extern person
Tilldelningsdatum2004 nov 12
Förlag
  • Ingrid Teige, I11 BMC, 221 84 Lund,
Tryckta ISBN91-268-6283-9
StatusPublished - 2004
PublikationskategoriForskning