CD8+ T-cells in psoriatic lesions preferentially use T-cell receptors V beta 3 and/or V beta 13.1 genes.

Autor: Chang JC; Immune Response Corporation, Carlsbad, California 92008, USA., Smith LR, Froning KJ, Schwabe BJ, Laxer JA, Caralli LL, Kurkland HH, Karasek MA, Wilkinson DI, Carlo DJ, et. al.
Jazyk: angličtina
Zdroj: Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 1995 Jul 07; Vol. 756, pp. 370-81.
DOI: 10.1111/j.1749-6632.1995.tb44541.x
Abstrakt: Restricted T-cell receptor V beta gene use in animal models of autoimmune disease has led to the development of strategies to treat autoimmune disease by targeting the T-cell receptors of the pathogenic T-cells. Restricted T-cell receptor gene use has been noted in human autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. We report here the finding of restricted T-cell receptor gene use in psoriasis vulgaris, as well. Our results show an elevated skin (over PBL) expression of V beta 3 and/or V beta 13.1 messages in the CD8+ T-cells in a majority of patients studied. CDR3 sequence analysis on these two V beta s from the skin demonstrated monoclonality or marked oligoclonality. A second biopsy performed 3.5 to 8 months later in four patients, at the same or different lesions, again revealed an elevated V beta 3 and/or V beta 13.1 expression and clonality. Moreover, in three of the four patients, the same TcR V beta CDR3 rearrangement was found in both biopsies, although there was no V beta CDR3 homology noted between patients. In two patients in which V beta 3 and/or V beta 13.1 was not elevated in the CD8+ T-cell population, an increase in V beta 17 gene use and clonality was found. 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. The effector function of these CD8+ T-cells is further supported by the clonality of TcR V beta sequence data, which indicates they are recruited and expanded in situ. The V beta s identified in this study are candidate targets for selective immunotherapeutic intervention in psoriasis.
Databáze: MEDLINE