02641nas a2200481 4500000000100000008004100001260001300042653001500055653001000070653000900080653002400089653001700113653001100130653000800141653001100149653001400160653001100174653002500185653002600210653001200236653000900248653001600257653002800273653004300301653001600344653002700360653000900387653001800396653001800414100001300432700001400445700001300459700001200472700001600484700001600500700001500516700001400531245022900545300001100774490000800785520135200793022001402145 2000 d c2000 Aug10aAdolescent10aAdult10aAged10aAmino Acid Sequence10aAntigens, CD10aBiopsy10aDNA10aFemale10aGranuloma10aHumans10aImmunohistochemistry10aKiller Cells, Natural10aleprosy10aMale10aMiddle Aged10aMolecular Sequence Data10aReceptors, Antigen, T-Cell, alpha-beta10aSarcoidosis10aSequence Analysis, DNA10aSkin10aSkin Diseases10aT-Lymphocytes1 aMempel M1 aFlageul B1 aSuarez F1 aRonet C1 aDubertret L1 aKourilsky P1 aGachelin G1 aMusette P00aComparison 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. a509-230 v1573 a

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.

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