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

Peripheral nerve damage is a major complication of reversal (or type-1) rea ctions in leprosy. The pathogenesis of nerve damage remains largely unresol ved, but detailed in situ analyses suggest that type-1 T cells play an impo rtant role. Mycobacterium leprae is known to have a remarkable tropism for Schwann cells of the peripheral nerve. Reversal reactions in leprosy are of ten accompanied by severe and irreversible nerve destruction and are associ ated with increased cellular immune reactivity against M. leprae. Thus, a l ikely immunopathogenic mechanism of Schwann cell and nerve damage in lepros y is that infected Schwann cells process and present Ags of M. leprae to Ag -specific, inflammatory type-1 T cells and that these T cells subsequently damage and lyse infected Schwann cells. Thus far it has been difficult to s tudy this directly because of the inability to grow large numbers of human Schwann cells. We now have established long-term human Schwann cell culture s from sural nerves and show that human Schwann cells express MHC class I a nd II, ICAM-1, and CD80 surface molecules involved in Ag presentation. Huma n Schwann cells process and present Al. leprae, as well as recombinant prot eins and peptides to MHC class II-restricted CD4(+) T cells, and are effici ently killed by these activated T cells. These findings elucidate a novel m echanism that is likely involved in the immunopathogenesis of nerve damage in leprosy.