CD8+ T-CELLS IN PSORIATIC LESIONS PREFERENTIALLY USE T-CELL RECEPTOR V(BETA)3 AND/OR V(BETA)13.1 GENES

被引:206
作者
CHANG, JCC [1 ]
SMITH, LR [1 ]
FRONING, KJ [1 ]
SCHWABE, BJ [1 ]
LAXER, JA [1 ]
CARALLI, LL [1 ]
KURLAND, HH [1 ]
KARASEK, MA [1 ]
WILKINSON, DI [1 ]
CARLO, DJ [1 ]
BROSTOFF, SW [1 ]
机构
[1] PSORIASIS RES INST,PALO ALTO,CA 94301
关键词
PSORIASIS; INFLAMMATION;
D O I
10.1073/pnas.91.20.9282
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Psoriasis is an inflammatory skin disorder characterized by epidermal keratinocyte hyperproliferation in association with a cellular infiltrate. There is evidence that activated T cells play a role in psoriatic plaque formation. We examined the T-cell receptor beta-chain variable gene segment (V-beta) use of epidermal T cells in shave biopsies of psoriatic lesions. Our results show increased expression of V (beta)3 and/or V (beta)13.1 messages in the CD8(+), but not CD4(+), T cells in the lesions of a majority of patients studied. Sequence analysis of complementarity-determining region 3 (CDR3) of these two V (beta) genes from the skin demonstrated monoclonality or marked oligoclonality. A second biopsy from the same or different lesions, performed 3.5-8 months later in four patients, again revealed increased V (beta)3 and/or V (beta)13.1 expression and clonality. Moreover, in three of the four patients, the same V (beta) CDR3 rearrangement was found in both biopsies, although there was no V (beta) CDR3 homology between patients. In two patients in which V (beta)3 and/or V (beta)13.1 was not increased, an increase in V (beta)17 gene use and clonality was found. The clonality of V (beta) sequence data indicates these cells are recruited and expanded in situ. The persistence of V (beta)3-and/or V (beta)13.1-bearing CD8(+) T cells in lesions that did not undergo resolution suggests their role as effector cells rather than as regulatory cells.
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收藏
页码:9282 / 9286
页数:5
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