Open AccessAnalysis of the cellular mechanism underlying inhibition of EAE after treatment with anti-NKG2A F(ab′) 2
Author(s) -
Jianmei W. Leavenworth,
Carola Schellack,
Hye-Jung Kim,
Linrong Lu,
Pieter Spee,
Harvey Cantor
Publication year - 2010
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0914732107
Subject(s) - experimental autoimmune encephalomyelitis , adoptive cell transfer , immunology , myelin oligodendrocyte glycoprotein , t cell , encephalomyelitis , microglia , chemistry , multiple sclerosis , biology , immune system , inflammation
Autoimmune encephalomyelitis may be ameliorated experimentally by enhancing NK cell-mediated elimination of activated autoreactive T cells through a mutation that interrupts the interaction between Qa-1b 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 IFNγ-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.