Analysis of the cellular mechanism underlying inhibition of EAE after treatment with anti-NKG2A F(ab′)2

作者：Leavenworth, Jianmei W.; Schellack, Carola; Kim, Hye-Jung; Lu, Linrong; Spee, Pieter; Cantor, Harvey^*

来源：Proceedings of the National Academy of Sciences, 2010, 107(6): 2562-2567.

DOI：10.1073/pnas.0914732107

• natural killer
• CD94
• Qa-1b
• multiple sclerosis

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.

• 出版日期2010-2-9
• 单位浙江大学