Novel mechanisms in the immunopathogenesis of leprosy nerve damage: The role of Schwann cells, T cells and Mycobacterium leprae

The major complication of reversal (or type 1) reactions in leprosy is peri pheral nerve damage. The pathogenesis of nerve damage remains largely unres olved. In situ analyses suggest an important role for type 1 T cells. Mycob acterium leprae is known to have a remarkable tropism for Schwann cells tha t surround peripheral axons. Reversal reactions in leprosy are often accomp anied by severe and irreversible nerve destruction and are associated with increased cellular immune reactivity against M. leprae. Thus, a likely immu nopathogenic mechanism of Schwann cell and nerve damage in leprosy is that infected Schwann cells process and present antigens of M. Leprae to antigen -specific, inflammatory type 1 T cells and that these T cells subsequently damage and lyse infected Schwann cells. Previous studies using rodent CD8() T cells and Schwann cells have revealed evidence for the existence of suc h a mechanism. Recently, a similar role has been suggested for human CD4(+) T cells. These cells may be more important in causing leprosy nerve damage in vivo, given the predilection of M. leprae for Schwann cells and the dom inant role of CD4(+) serine esterase(+) Th1 cells in leprosy lesions. Antag onism of molecular interactions between M. leprae, Schwann cells and inflam matory T cells may therefore provide a rational strategy to prevent Schwann cell and nerve damage in leprosy.