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Monoclonal Antibody against T‐Cell Receptor α β Induces Self‐Tolerance in Chronic Experimental Autoimmune Encephalomyelitis
Author(s) -
Lavasani S.,
Dzhambazov B.,
Andersson M.
Publication year - 2007
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2006.01866.x
Subject(s) - experimental autoimmune encephalomyelitis , immunology , t cell , t cell receptor , cd8 , monoclonal antibody , adoptive cell transfer , encephalomyelitis , biology , population , antibody , medicine , antigen , immune system , multiple sclerosis , environmental health
The therapeutic effect of monoclonal antibody (H57‐597 MoAb) against T‐cell receptor (TCR) α β 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 α β immediately after immunization protected the mice from EAE. Furthermore, anti‐TCR α β 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‐ α and IFN‐ γ . 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 α β MoAb (H57‐597), which represents a promising approach in treatment of T‐cell‐mediated autoimmune diseases.