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(American Journal of Pathology. 2000;157:509-523.)
© 2000 American Society for Investigative Pathology

Regular Articles

Comparison of the T Cell Patterns in Leprous and Cutaneous Sarcoid Granulomas

Presence of V{alpha}24-Invariant Natural Killer T Cells in T-Cell-Reactive Leprosy Together with a Highly Biased T Cell Receptor V{alpha} Repertoire

Martin Mempel*{dagger}, Beatrice Flageul{dagger}, Felipe Suarez*, Catherine Ronet*, Louis Dubertret{dagger}, Philippe Kourilsky*, Gabriel Gachelin* and Philippe Musette*{dagger}

From the Institut Pasteur,*
Unité de Biologie Moléculaire du Gène, INSERM U277, Département d’Immunologie, Paris; and the Institut de Recherche sur la Peau,{dagger}
INSERM U312, l’Hôpital St.-Louis, Paris, France

The T-cell-reactive (eg, tuberculoid and reversal) forms of leprosy represent a well-defined granulomatous reaction pattern against an invading pathogen. The immune response in cutaneous sarcoidosis is a granulomatous condition that pathologically is very similar to T-cell reactive leprosy. However, it lacks a defined causative agent. In view of the role of NKT cells in murine granulomas induced by mycobacterial cell walls, we have searched for the presence of NKT cells in the cutaneous lesions of both leprosy and sarcoidosis. These cells were present in T-cell-reactive leprosy but were undetectable in cutaneous sarcoidosis. We have also studied the TCR V{alpha} repertoire in the two diseases. In addition to V{alpha}24+ NKT cells, all patients with T-cell-reactive leprosy showed a very restricted T-cell-reactive V{alpha} repertoire with a strong bias toward the use of the V{alpha}6 and V{alpha}14 segments. V{alpha}6 and V{alpha}14+ T cells were polyclonal in terms of CDR3 length and J{alpha} usage. In contrast, most sarcoidosis patients showed a diverse usage of V{alpha} chains associated with clonal or oligoclonal expansions reminiscent of antigen-driven activation of conventional T cells. Thus the origin and perpetuation of the two kinds of granulomatous lesions appear to depend on altogether distinct T-cell recruiting mechanisms.




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