Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 6, Pages 2562-2567Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0914732107
Keywords
natural killer; CD94; Qa-1b; multiple sclerosis
Categories
Funding
- NIH [AI 037562]
- Novo Nordisk [T32 CA070083]
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Autoimmune encephalomyelitis may be ameliorated experimentally by enhancing NK cell-mediated elimination of activated auto-reactive T cells through a mutation that interrupts the interaction between Qa-1(b) and CD94/NKG2A. Here we evaluate the ability of an anti-NKG2A F(ab')(2) Ab to enhance elimination of autoreactive T cells and reduce experimental autoimmune encephalomyelitis (EAE). Anti-NKG2A F(ab')(2) treatment diminishes progression of both myelin oligodendrocyte glycoprotein (MOG)-induced EAE in intact C57BL/6 mice and after adoptive transfer of disease-causing T cells. Analyses of the underlying mechanism revealed that administration of anti-NKG2A F(ab')(2) Ab reduces CD4(+) T recall responses to MOG and skews the proportion of IL-17- and IFN gamma-producing CD4(+) T cells toward the protective IL-4- and IL-10-secreting CD4(+) T cell subpopulations. CD94/NKG2A-dependent inhibition of inflammatory damage to spinal cord is associated with decreased infiltration of T cells and reduced microglia activation in the central nervous system. Because anti-NKG2A F(ab')(2) treatment had no detectable effect on the numbers or activity of T and B lymphocytes and NK cells in peripheral lymphoid tissues, this anti-NKG2A-based approach may represent a safe and effective therapy for this CNS disorder.
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