Comparison of the T cell patterns in leprous and cutaneous sarcoid granulomas. Presence of Valpha24-invariant natural killer T cells in T-cell-reactive leprosy together with a highly biased T cell receptor Valpha repertoire.
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 Valpha repertoire in the two diseases. In addition to Valpha24(+) NKT cells, all patients with T-cell-reactive leprosy showed a very restricted T-cell-reactive Valpha repertoire with a strong bias toward the use of the Valpha6 and Valpha14 segments. Valpha6 and Valpha14(+) T cells were polyclonal in terms of CDR3 length and Jalpha usage. In contrast, most sarcoidosis patients showed a diverse usage of Valpha 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.
Mempel
M
M
Institut Pasteur, Unité de Biologie Moléculaire du Gène, INSERM U277, Département d'Immunologie, Paris. INSERM U312, l'Hôpital St. -Louis, Paris, France.
Flageul
B
B
Suarez
F
F
Ronet
C
C
Dubertret
L
L
Kourilsky
P
P
Gachelin
G
G
Musette
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000032:analysis; D001706:Biopsy; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D006099:Granuloma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007918:Leprosy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D012507:Sarcoidosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017422:Sequence Analysis, DNA; D012867:Skin / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D012871:Skin Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA