Monoclonal Antibody against T-Cell Receptor alphabeta Induces Self-Tolerance in Chronic Experimental Autoimmune Encephalomyelitis.

Lavasani, ShahramLund University,Lunds universitet,Funktionell zoologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Functional zoology,Department of Biology,Faculty of Science (författare)

The therapeutic effect of monoclonal antibody (H57-597 MoAb) against T-cell receptor (TCR) alpha beta has been investigated on MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE), as a model system for T-cell-mediated chronic inflammation in the central nervous system (CNS). Short-term administration of the anti-TCR alpha beta immediately after immunization protected the mice from EAE. Furthermore, anti-TCR alpha beta treatment on an established disease restored the self-tolerance which led to a complete remission of EAE and a dramatic reduction of inflammatory cells in the CNS, while treatment with control antibody (hamster IgG) was ineffective. The remission was durable and not associated with disappearance of autoreactive T cells as measured by persistence of MOG-reactive T-cell proliferation in vitro. However, MOG-reactive T cells from anti-TCR-treated animals produced significantly lower amounts of inflammatory TNF-alpha and IFN-gamma. In addition, while a transient deletion of CD4(+) and CD8(+) T cells was observed, a population of T cells expressing CD3, NK1.1 and CD69 (NKT cells) were expanding. By transfer of spleen cells from anti-TCR MoAb-treated animals, we could show that the tolerogenic capacity can be transferred to untreated recipients with EAE. The data indicate therapeutic effect of anti-TCR alpha beta MoAb (H57-597), which represents a promising approach in treatment of T-cell-mediated autoimmune diseases.

Dzhambazov, BalikLund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups(Swepub:lu)infl-bdz (författare)
Andersson, M (författare)
Funktionell zoologiBiologiska institutionen (creator_code:org_t)

Ingår i:Scandinavian Journal of Immunology: Wiley65:1, s. 39-471365-30830300-9475

Av författaren/redakt...: Lavasani, Shahra ...; Dzhambazov, Bali ...; Andersson, M

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