TY - JOUR
T1 - Single dose of glycoengineered anti-CD19 antibody (MEDI551) disrupts experimental autoimmune encephalomyelitis by inhibiting pathogenic adaptive immune responses in the bone marrow and spinal cord while preserving peripheral regulatory mechanisms
AU - Chen, Ding
AU - Blazek, Monica
AU - Ireland, Sara
AU - Ortega, Sterling
AU - Kong, Xiangmei
AU - Meeuwissen, Anouk
AU - Stowe, Ann
AU - Carter, Laura
AU - Wang, Yue
AU - Herbst, Ronald
AU - Monson, Nancy L.
N1 - Publisher Copyright:
© 2014 by The American Association of Immunologists, Inc.
PY - 2014/11/15
Y1 - 2014/11/15
N2 - Plasma cells and the autoreactive Abs they produce are suspected to contribute to the pathogenesis of multiple sclerosis, but recent attempts to target these components of humoral immunity have failed. MEDI551, an anti-CD19 Ab that depletes mature B cells including plasma cells may offer a compelling alternative that reduces pathogenic adaptive immune responses while sparing regulatory mechanisms. Indeed, our data demonstrate that a single dose of MEDI551, given before or during ongoing experimental autoimmune encephalomyelitis, disrupts development of the disease. Leukocyte infiltration into the spinal cord is significantly reduced, as well as short-lived and long-lived autoreactive CD138+ plasma cells in the spleen and bone marrow, respectively. In addition, potentially protective CD1dhiCD5+ regulatory B cells show resistance to depletion, and myelin-specific Foxp3+ regulatory T cells are expanded. Taken together, these results demonstrate that MEDI551 disrupts experimental autoimmune encephalomyelitis by inhibiting multiple proinflammatory components whereas preserving regulatory populations.
AB - Plasma cells and the autoreactive Abs they produce are suspected to contribute to the pathogenesis of multiple sclerosis, but recent attempts to target these components of humoral immunity have failed. MEDI551, an anti-CD19 Ab that depletes mature B cells including plasma cells may offer a compelling alternative that reduces pathogenic adaptive immune responses while sparing regulatory mechanisms. Indeed, our data demonstrate that a single dose of MEDI551, given before or during ongoing experimental autoimmune encephalomyelitis, disrupts development of the disease. Leukocyte infiltration into the spinal cord is significantly reduced, as well as short-lived and long-lived autoreactive CD138+ plasma cells in the spleen and bone marrow, respectively. In addition, potentially protective CD1dhiCD5+ regulatory B cells show resistance to depletion, and myelin-specific Foxp3+ regulatory T cells are expanded. Taken together, these results demonstrate that MEDI551 disrupts experimental autoimmune encephalomyelitis by inhibiting multiple proinflammatory components whereas preserving regulatory populations.
UR - http://www.scopus.com/inward/record.url?scp=84910150823&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1401478
DO - 10.4049/jimmunol.1401478
M3 - Article
C2 - 25281717
AN - SCOPUS:84910150823
SN - 0022-1767
VL - 193
SP - 4823
EP - 4832
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -