Suppression of murine experimental autoimmune encephalomyelitis by interleukin-2 receptor targeted fusion toxin, DAB(389)IL-2.

Publication/Presentation Date

1-1-2010

Abstract

Previously we have shown that DAB(389)IL-2, a recombinant fusion toxin targeting IL-2R bearing cells, suppressed disease in the rat experimental autoimmune encephalomyelitis (EAE) model of acute multiple sclerosis (MS). Our present study demonstrates that DAB(389)IL-2 can also effectively suppress acute (A)-EAE, relapsing (R)-EAE and chronic (C)-EAE in mouse demyelinating models. DAB(389)IL-2 significantly suppressed mitogenic proliferation of spleen cells while mutant fusion proteins DA(glu53)B(389)IL-2 and DAB(389)IL-2(8-10) did not. EAE was successfully suppressed when DAB(389)IL-2 was administered in various regimens between days 1 and 15 post immunization in all three models. CD4(+)IL-2R(+) cells were reduced in the spleen but not in the lymph nodes of DAB(389)IL-2-treated mice during A-EAE while the number of CD8(+) cells was unchanged. DAB(389)IL-2 also significantly reduced the number of CD4(+), CD8(+), CD25(+), TCRgammadelta(+) phenotype and CD11b(+) macrophages/microglia within spinal cord lesions. These data strongly suggest that DAB(389)IL-2 specifically targeted myelin protein-activated CD4(+) T cells and strengthens the argument for the use of DAB(389)IL-2 in treatment strategies for MS.

Volume

261

Issue

2

First Page

144

Last Page

152

ISSN

1090-2163

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

20042183

Department(s)

Administration and Leadership

Document Type

Article

Link to Full Text

Share

COinS