HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Spierings, E. Articles by Ottenhoff, T. H. M. Search for Related Content PubMed PubMed Citation Articles by Spierings, E. Articles by Ottenhoff, T. H. M.

Mycobacterium leprae-Specific, HLA Class II-Restricted Killing of Human Schwann Cells by CD4⁺ Th1 Cells: A Novel Immunopathogenic Mechanism of Nerve Damage in Leprosy¹

Eric Spierings^2,*, Tjitske de Boer^*, Brigitte Wieles^*, Linda B. Adams, Enrico Marani^, and Tom H. M. Ottenhoff^*

^* Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands; National Hansen’s Disease Center Laboratory Research Branch, Louisiana State University, Baton Rouge, LA 70894; Department of Polymer Chemistry and Biomaterials, Institute for Biomedical Technology, University of Twente, Enschede, The Netherlands; and Department of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands

Peripheral nerve damage is a major complication of reversal (or type-1) reactions in leprosy. The pathogenesis of nerve damage remains largely unresolved, but detailed in situ analyses suggest that type-1 T cells play an important role. Mycobacterium leprae is known to have a remarkable tropism for Schwann cells of the peripheral nerve. Reversal reactions in leprosy are often accompanied 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 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 study this directly because of the inability to grow large numbers of human Schwann cells. We now have established long-term human Schwann cell cultures from sural nerves and show that human Schwann cells express MHC class I and II, ICAM-1, and CD80 surface molecules involved in Ag presentation. Human Schwann cells process and present M. leprae, as well as recombinant proteins and peptides to MHC class II-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 immunopathogenesis of nerve damage in leprosy.

This article has been cited by other articles:

				J. S. Im, N. Tapinos, G.-T. Chae, P. A. Illarionov, G. S. Besra, G. H. DeVries, R. L. Modlin, P. A. Sieling, A. Rambukkana, and S. A. Porcelli Expression of CD1d Molecules by Human Schwann Cells and Potential Interactions with Immunoregulatory Invariant NK T Cells J. Immunol., October 15, 2006; 177(8): 5226 - 5235. [Abstract] [Full Text] [PDF]

				D. A. Hagge, N. A. Ray, J. L. Krahenbuhl, and L. B. Adams An In Vitro Model for the Lepromatous Leprosy Granuloma: Fate of Mycobacterium leprae from Target Macrophages after Interaction with Normal and Activated Effector Macrophages J. Immunol., June 15, 2004; 172(12): 7771 - 7779. [Abstract] [Full Text] [PDF]

				R. B. Oliveira, M. T. Ochoa, P. A. Sieling, T. H. Rea, A. Rambukkana, E. N. Sarno, and R. L. Modlin Expression of Toll-Like Receptor 2 on Human Schwann Cells: a Mechanism of Nerve Damage in Leprosy Infect. Immun., March 1, 2003; 71(3): 1427 - 1433. [Abstract] [Full Text] [PDF]