Mycobacterium leprae-Specific,HLA Class II-Restricted Killing of Human Schwann Cells by CD4~+ Th1 Cells:A Novel Immunopathogenic Mechanism of Nerve Damage in Leprosy

摘要

Peripheral nerve damage is a major complication of reversal (or type-i) reactions in leprosy. The pathogenesis of nerve damage umins largely unresolved, but detailed in situ analyses suggest that type-i T cells play an important role. Mycobacterium leprae ~ known to have a remarkable tropism for Schwann cells of the peripheral nerve. Reversal reactions in leprosy are often mmnpanied by severe and irreversible nerve destruction and are associated with increased cellular immune reactivity against M. leprae.Thus, a likely immunopathogenic mechanism of Schwann cell and nerve damage in leprosy is that infected Schwann cells ~s and present Ags of M. leprae to Ag-specific, inflammatory type-i T cells and that these T cells subsequently damage and hfected Schwann cells. Thus far it has been difficult to study this directly because of the inability to grow large numbers of i Schwann cells. We now have established long-term human Schwann cell cultures from sural nerves and show that human wnn cells express MHC class I and II, ICAM-1, and CD8O surface molecules involved in Ag presentation. Human Schwann process and present M. leprae, as well as recombinant proteins and peptides to MHC class TI-restricted CD4~+T cells, and are efficiently killed by these activated T cells. These findings elucidate a novel mechanism that is likely involved in the immu-nopathogenesis of nerve damage in leprosy.