期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：6
页码：2562-2567
DOI：10.1073/pnas.0914732107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 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.
